Systems and methods of de-endothelialization

ABSTRACT

Apparatus and methods for treating a wall of an aneurysm formed in a vessel includes introducing a tubular member into the body lumen until a distal end of the tubular member is located within the aneurysm. A fluid is delivered via a lumen of the tubular member into the aneurysm to at least partially de-endothelialize the wall of the aneurysm, thereby causing an endothelium of the wall to generate fibrous tissue to strengthen the wall of the aneurysm.

RELATED APPLICATION DATA

The present application is a continuation of pending U.S. patentapplication Ser. No. 10/357,572, filed Feb. 3, 2003, the priority ofwhich is claimed under 35 U.S.C. §120, and the contents of which isincorporated herein by reference in its entirety, as though set forth infull.

FIELD OF THE INVENTION

The field of the invention pertains to embolizing blood vessels oraneurysms, and more particularly, to systems and methods for reducingblood vessel or aneurysm recanalization.

BACKGROUND

In many clinical situations, blood vessels are occluded for a variety ofpurposes, such as to control bleeding, to prevent blood supply totumors, to stop blood flow to arterio-venous malformations or fistulas,and to block blood flow within an aneurysm.

Embolization of blood vessels is particularly useful in treatinganeurysms. Aneurysms are abnormal blood-filled dilations of a bloodvessel wall that may rupture causing significant bleeding. For the casesof intracranial aneurysms, the significant bleeding may lead to damageto surrounding brain tissue or death. Intracranial aneurysms may bedifficult to treat when they are formed in remote cerebral bloodvessels, which are very difficult to access. If left untreated,hemodynamic forces of normal pulsatile blood flow can rupture fragiletissue in the area of the aneurysm causing a stroke.

Vaso-occlusive devices have been used to treat aneurysms. Vaso-occlusivedevices are surgical implants placed within blood vessels or vascularcavities, typically using a catheter, to form a thrombus and occlude thesite. For instance, a stroke or other such vascular accident may betreated by placing a vaso-occlusive device proximal of the site to blockthe flow of blood to the site and alleviate the leakage. An aneurysm maysimilarly be treated by introducing a vaso-occlusive device through theneck of the aneurysm. The thrombogenic properties of the vaso-occlusivedevice cause a mass to form in the aneurysm and alleviate the potentialfor growth of the aneurysm and its subsequent rupture. Other diseases,such as tumors, may often be treated by occluding the blood flow to thetumor.

There are a variety of vaso-occlusive devices suitable for formingthrombi. One such device is found in U.S. Pat. No. 4,994,069, toRitchart et al., the entirety of which is expressly incorporated byreference herein. That patent describes a vaso-occlusive coil thatassumes a linear helical configuration when stretched and a foldedconvoluted configuration when relaxed. The stretched configuration isused to deliver the coil to the desired site and the convolutedconfiguration occurs when the coil is ejected from the catheter and thecoil relaxes. Ritchart et al. describes a variety of shapes, including“flower” shapes and double vortices. A random shape is described aswell.

U.S. Pat. No. 6,280,457B1 to Wallace et al., describes an occlusivedevice comprising an inner core wire covered with a polymer. Thepolymeric material includes protein based polymers, absorbable polymers,non-protein based polymers, and combinations thereof. The polymer maycontribute to forming emboli for occluding a body cavity.

Vaso-occlusive coils having complex, three-dimensional structures in arelaxed configuration are described in U.S. Pat. No. 6,322,576B1 toWallace et al. The coils may be deployed in the approximate shape of asphere, an ovoid, a clover, a box-like structure or other distortedspherical shape. The patent also describes methods of winding theanatomically shaped vaso-occlusive device into appropriately shapedforms and annealing them to form various devices.

Vaso-occlusive coils having little or no inherent secondary shape havealso been described. For instance, co-owned U.S. Pat. Nos. 5,690,666 and5,826,587 by Berenstein et al., describe coils having little or no shapeafter introduction into the vascular space.

Vaso-occlusive devices work initially by slowing blood flow inside theaneurysm. As a result of the slowed blood flow, the blood inside theaneurysm clots. The combination of the vaso-occlusive devices and theclot protects the aneurysm from hemodynamic forces (i.e., forces on theaneurysm wall due to blood flow) that may cause recanalization andrecurrence of the aneurysm. However, recanalization and recurrence ofthe aneurysm may still occur for various reasons. For example, thevaso-occlusive device may rearrange itself due to the hemodynamicforces. Typically, the vaso-occlusive device(s) near the neck of theaneurysm is most affected by the effects of blood flow. Also, the clotformed may break down due to the hemodynamic forces and/or naturalchemical processes. This is more likely to occur if the aneurysm isloosely packed with vaso-occlusive devices.

Accordingly, devices and methods for reducing recanalization orrecurrence of an aneurysm would be useful.

SUMMARY OF THE INVENTION

The present invention is directed to apparatus and methods for treatinganeurysms or other body cavities. More particularly, the presentinvention is directed to apparatus and methods for disrupting theendothelium of the wall of an aneurysm to reduce the risk of the wallexpanding, thinning, and/or or rupturing, or to reduce the risk ofrecanalization of a body cavity, such as an arterio-venous malformation,fistula, or other blood vessel.

In accordance with one aspect of the present invention, an apparatus fordisrupting an endothelium of an aneurysm or other body lumen wall isprovided. Generally, the apparatus includes an elongate member includinga proximal end and a distal end configured for insertion into a bodylumen of a patient. The distal end of the elongate member may have aprimary shape, e.g., a substantially linear relaxed shape, a curvilinearrelaxed shape, and/or a helical coil shape. Optionally, the elongatemember may have a secondary shape, e.g., a three-dimensional shapetowards which the elongate member may be biased in a relaxed state freefrom external forces. The elongate member may be formed from an elasticor superelastic material and/or a bioabsorbable material.

Any of the apparatus described herein may include a delivery device,e.g., a sheath, catheter or other tubular member, for delivering theelongate member. For example, the distal end of the elongate member maybe disposed within a lumen of the tubular member as a distal end of thetubular member is advanced to a treatment site, e.g., to prevent thedistal end from contacting tissue prematurely, i.e., until deployed.

Optionally, the distal end of the elongate member may be deployable suchthat the distal end may remain within the aneurysm or other body cavityupon completing the procedure. The distal end of the elongate member maybe deployable using a mechanical joint, an electrolytic joint, and/or adissolvable adhesive. In addition or alternatively, the distal end ofthe elongate member may be steerable, e.g., to guide the distal endaround bends, into a body cavity, such as an aneurysm sac, and/orotherwise manipulating the distal end during a procedure.

In one embodiment, one or more abrasive elements are carried on thedistal end of the elongate member for disrupting the endothelium of theaneurysm or other body cavity. The abrasive element(s) may includehooks, needles, fins, saw tooth elements, and/or sharp particles. Theabrasive element(s) that may be disposed on an entire exposed surface ofthe distal end of the elongate member or may be selectively disposed ina pattern on only a portion of the distal end. Preferably, the abrasiveelement(s) has(have) a size and stiffness for disrupting the endotheliumof a vessel wall, e.g., a wall of an aneurysm, without substantial riskof penetrating completely through the wall.

Optionally, an expandable member may be carried by the distal end of theelongate member, the abrasive elements being carried on the expandablemember. For example, the expandable member may be an expandable basketincluding one or more splines, each carrying one or more abrasiveelements. Alternatively, the expandable member may be an elastic orinelastic balloon that may be expanded upon introducing fluid into aninterior of the balloon. If the elongate member includes an expandablemember, the expandable member may be collapsed when disposed within adelivery device, e.g., a sheath or other tubular member. The expandablemember may be biased to expand towards an expanded configuration whendeployed from the delivery device or may be controllably expanded, e.g.,mechanically or using a fluid. In addition, the balloon may be porousand/or may include one or more openings or lumens for delivering afluid, e.g., a de-endothelialization fluid beyond an outer surface ofthe balloon, as explained further below.

An apparatus, such as those described above, may be used forde-endothelializing an aneurysm. Initially, an apparatus may be providedthat includes an elongate member carrying one or more abrasive elementson its distal end. The distal end may be introduced into a body lumen,e.g., a patient's vasculature, and advanced until the distal end reachesa target site intended for treatment, e.g., an aneurysm within acerebral or other artery. The distal end may be provided within acatheter or other delivery device to protect the vasculature from beingdamaged by the abrasive elements and/or to protect the distal end of theelongate member.

For example, a delivery catheter may be positioned adjacent an aneurysm,and the distal end of the elongate member may be advanced from a lumenof the catheter into the aneurysm. The distal end of the elongate membermay be manipulated, e.g., advanced, retracted, steered, and/or rotatedto engage the abrasive elements with the wall of the aneurysm to disruptthe endothelium of the wall. If an expandable member is carried on thedistal end, the expandable member may be expanded to enhance engagingthe endothelium with the abrasive elements. Consequently, the patient'sbody may react to the disruption by generating fibrous tissue, e.g.,scar tissue, that may thicken or otherwise strengthen the wall of theaneurysm, thereby substantially reducing the risk of the wall thinningfurther and/or the aneurysm growing or rupturing.

The elongate member may then be retracted into the catheter and bothremoved from the patient. Alternatively, the distal end of the elongatemember may be released from the elongate member to at least partiallyfill the aneurysm.

In accordance with another aspect of the present invention, anotherapparatus for disrupting an endothelium of an aneurysm or other bodycavity wall is provided that uses thermal energy to disrupt theendothelium. Similar to the previous embodiments, the apparatus mayinclude an elongate member having a distal end, which may be steerableand/or deployable, as described above. A thermal element may be carriedby the distal end of the elongate member that is configured for beingheated or cooled to a de-endothelializing temperature. Similar to theprevious embodiment, the distal end may include an expandable member,e.g., an expandable basket or balloon, that may carry the heating orcooling element.

In one form, the thermal element may be an electrically resistiveheating element that may be coupled to a source of electrical energy.Upon delivering electrical energy to the distal end, the resistiveheating element may become heated sufficiently to disrupt theendothelium that it contacts directly or that is heated by conductionand/or convection. Alternatively, the thermal element may be an energystorage element that may be heated or cooled before being insertedthrough a thermally insulated delivery device, e.g., a sheath, that hasbeen placed adjacent the aneurysm.

In a further alternative, the thermal element may be an expandableballoon or other hollow element. The hollow element may be filled with aheated or cooled fluid to heat or cool the hollow element to a desiredtemperature for de-endothelializing the wall of an aneurysm that itcontacts directly or to which it is coupled by conduction or convection.Optionally, the hollow element may include one or more openings suchthat the heated or cooled fluid may be delivered from the hollow elementinto the aneurysm or body cavity to disrupt the endothelium of the wall.In this embodiment, the elongate member and/or the delivery device mayinclude a sealing member that may be used to at least partially seal theaneurysm or a body lumen communicating with the aneurysm.

These embodiments may be used to disrupt the endothelium of an aneurysmor other body cavity wall using thermal energy. The distal end of theelongate member may be advanced from a delivery device, such as a sheathor catheter, into the aneurysm. For example, the delivery device may beadvanced through the patient's vasculature with the elongate membertherein. Once the delivery device is adjacent to the aneurysm, thedistal end of the elongate member may be advanced from the deliverydevice to place the thermal element within the aneurysm.

If the thermal element includes an electrically resistive heatingelement, electrical energy may be delivered to the heating element,thereby heating the interior of the aneurysm and/or heating the wallcontacted by the heating element until the endothelium is disrupted.Alternatively, if the thermal element includes an expandable member, theexpandable member may be expanded within the aneurysm to at leastpartially fill the aneurysm cavity.

In addition or alternatively, if the thermal element is porous orincludes outlet ports coupled to a source of heated or cooled fluid viaa lumen, the fluid may be delivered into the aneurysm to disrupt theendothelium. Optionally, a sealing member may be located proximal to thethermal element that may be expanded or otherwise engaged with the neckof the aneurysm to substantially seal the aneurysm. This may preventfluid delivered into the aneurysm from escaping into adjacent bodylumen(s). Preferably, the fluid is heated to a temperature above fiftydegrees Celsius (50° C.) or cooled to a temperature below zero degreesCelsius (0° C.).

In accordance with yet another aspect of the present invention, a methodis provided for treating a wall of an aneurysm, arterio-venousmalformation, fistula, or other a body lumen. A tubular member may beintroduced into the vasculature until a distal end of the tubular memberis located within the aneurysm or blood vessel. A fluid may be deliveredvia a lumen of the tubular member into the aneurysm or blood vessel toat least partially de-endothelialize the wall of the aneurysm or bloodvessel. This may cause an endothelium of the wall to generate fibroustissue to strengthen the wall of the aneurysm or to strengthen and/orocclude the blood vessel.

In one embodiment, a sealing member may be carried by one of the innerand outer members, and the sealing member may be engaged with a neck ofthe aneurysm to substantially sealing the aneurysm before the fluid isdelivered into the aneurysm. In an exemplary embodiment, the sealingmember may include an annular shaped member including an outer wall anda passage extending therethrough, and wherein the annular shaped memberpositioned such that the outer wall is disposed adjacent the neck of theaneurysm to substantially seal the aneurysm and the passage is disposedcoaxially within the body lumen to allow continued fluid flow along thebody lumen.

In addition or alternatively, the tubular member may include a ballooncarried on the distal end thereof, and wherein the fluid is deliveredvia the balloon. For example, the balloon may include one or moreopenings extending through a wall of the balloon and communicating withan interior of the balloon, the fluid being delivered into the aneurysmthrough the one or more openings. In one embodiment, the fluid may beintroduced into the interior of the balloon, thereby expanding theballoon until the one or more openings expand sufficiently to allow thefluid to exit from the interior of the balloon through the one or moreopenings. Alternatively, the balloon may include a delivery lumen formedwithin a wall of the balloon and the fluid may be delivered into theaneurysm through the delivery lumen. In another alternative, the balloonmay carry one or more abrasive elements configured for disrupting theendothelium of the wall of the aneurysm, as described above.

In accordance with yet another aspect of the present invention, a methodis provided for treating a wall of an aneurysm, blood vessel, or otherbody lumen. A tubular member may be introduced into the body lumen untila distal end of the tubular member is located adjacent the aneurysm, thedistal end carrying an annular shaped member. The annular shaped membermay be expanded until an outer wall of the annular shaped member engagesa neck of the aneurysm to substantially seal the aneurysm, the annularshaped member including a passage extending therethrough to allowcontinued fluid flow along the body lumen. A fluid may be delivered intothe aneurysm to at least partially de-endothelialize the wall of theaneurysm, thereby causing an endothelium of the wall to generate fibroustissue to strengthen the wall of the aneurysm.

In accordance with still another aspect of the present invention, anapparatus is provided for disrupting an endothelium of an aneurysm orother body lumen that includes an outer member including a proximal endand a distal end having a size and shape for insertion into a body lumencommunicating with an aneurysm or other body lumen. An inner member maybe deployable from within the outer member that includes a proximal end,a distal end having a size and shape for insertion into an aneurysmcavity or body lumen, and a lumen extending between the proximal end andan outlet port on the distal end. A source of de-endothelializationfluid may be coupled to the proximal end of the tubular member andcommunicating with the first lumen. A sealing member may be carried byone of the inner and outer members proximal to the outlet port, thesealing member having a size and shape for substantially sealing a neckof the aneurysm or other body lumen.

In accordance with yet another aspect of the present invention, a methodis provided for treating a malformation extending from a body lumen,such as an arterio-venous malformation or fistula. A tubular member maybe introduced into the body lumen until a distal end of the tubularmember is located within the malformation. The malformation may besubstantially sealed from the body lumen, and fluid aspirated fromwithin the malformation. For example, the malformation may be flushedwith fluid, such as saline, and excess fluid may be aspirated from themalformation to substantially clear the malformation. Preferably, themalformation is flushed and aspirated substantially simultaneously.

In one embodiment, the malformation may be substantially sealed form thebody lumen by expanding an occlusion member carried on the distal end ofthe tubular member to engage an entrance into the malformation. Inanother embodiment, an occlusion member, such as a compliant balloon,may be introduced into the body lumen until the occlusion member isadjacent the malformation and then expanded to engage an entrance to themalformation.

A therapeutic fluid may be delivered via the tubular member into themalformation, e.g., to at least partially de-endothelialize anendothelium of the malformation. In addition or alternatively, thetherapeutic fluid may cause at least one of the following to occurwithin the malformation: cellular lysis, disruption of cellular orintercellular adhesions, and disruption of cellular function.Thereafter, the therapeutic fluid may be aspirated from themalformation, e.g., by simultaneous flushing and aspirating. If one ormore occlusion members were used to seal malformation, the occlusionmember(s) may be collapsed or otherwise removed from the body lumen,allowing the malformation to communicate with the body lumen.

Where the malformation is an arterio-venous malformation or fistula,e.g., extending between an artery and a vein or two other blood vessels,an occlusion may be introduced into the artery or first vessel tosubstantially isolate the artery or first vessel from the arterio-venousmalformation. Another occlusion member may be introduced into the veinor second vessel to substantially isolate the vein or second vessel fromthe arterio-venous malformation. Thus, the malformation may besubstantially isolated from both vessels, e.g., to allow flushing,aspiration, and/or therapeutic fluid infusion only within themalformation. Where infusion and aspiration are simultaneous, one of theocclusion members may be used for infusion, while the other occlusionmember may be used for aspiration.

In accordance with still another aspect of the present invention, anapparatus is provided for disrupting an endothelium of a wall of ananeurysm or other body lumen that includes an elongate core memberhaving an outer surface, a proximal end, and a distal end having a sizeand shape for introduction into an aneurysm or other body lumen. One ormore fibers are provided on the outer surface of the core member, theone or more fibers carrying a de-endothelialization agent.

The apparatus may be used to at least partially de-endothelialize a wallof an aneurysm or other body lumen. The core member may be introducedinto the aneurysm or other body lumen, thereby releasing the fluid fromthe one or more fibers within the aneurysm or other body lumen, thefluid disrupting at least a portion of the endothelium of the wall ofthe aneurysm or other body lumen. The core member may be dipped in asource of de-endothelialization fluid such that the one or more fibersabsorb the fluid.

Alternatively, the core member may include a coating, e.g., a hydrogel,on the outer surface of the core member that is degradable when exposedto bodily fluid, the coating including a de-endothelialization agentthat is released as the degrades.

To at least partially de-endothelialize a wall of an aneurysm or otherbody lumen, the core member may be introduced into the aneurysm. Thecore member may be left within the aneurysm or other body lumen untilthe coating at least degrades to release the de-endothelialization agentwithin the aneurysm or other body lumen, whereby the agent may at leastpartially de-endothelialize a wall of the aneurysm or other body lumen.

Other objects and features of the present invention will become apparentfrom consideration of the following description taken in conjunctionwith the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate the design and utility of preferred embodimentsof the present invention, in which similar elements are referred to bycommon reference numerals. In order to better appreciate how theadvantages and objects of the present inventions are obtained, a moreparticular description of the present inventions briefly described abovewill be rendered by reference to specific embodiments thereof, which areillustrated in the accompanying drawings. Understanding that thesedrawings depict only typical embodiments of the invention and are nottherefore to be considered limiting of its scope, the invention will bedescribed and explained with additional specificity and detail throughthe use of the accompanying drawings.

FIG. 1 is a side view of a de-endothelialization device.

FIG. 2A-2F are details of the de-endothelialization device of FIG. 1,showing various embodiments of an abrasive element.

FIGS. 3-11 are exemplary secondary shapes of the de-endothelializationdevice of FIG. 1.

FIG. 12 is a partial cross-sectional side view of a catheter fordelivering a de-endothelialization device into an aneurysm.

FIG. 13 is a partial cross-sectional side view of a catheter deliveringa de-endothelialization device therefrom.

FIG. 14 is a partial cross-sectional side view of a catheter deliveringanother de-endothelialization device therefrom.

FIG. 15 is a partial cross-sectional side view of a catheter deliveringyet another de-endothelialization device therefrom, showing thede-endothelialization device adopting a secondary shape as it isdeployed.

FIG. 16 is a partial cross-sectional detail of a de-endothelializationdevice coupled to a core wire by a mechanical joint.

FIG. 17 is a partial cross-sectional detail of a de-endothelializationdevice coupled to a core wire by an electrolytic link.

FIG. 18 is a partial cross-sectional side view of ade-endothelialization device coupled to a core member and being deployedfrom a delivery catheter.

FIG. 19 is a partial cross-sectional side view of an alternativeembodiment of the de-endothelialization device of FIG. 18, showing thede-endothelialization device having a curvilinear relaxed shape.

FIG. 20 is a partial cross-sectional side view of another alternativeembodiment of the de-endothelialization device of FIG. 18, showing thede-endothelialization device having a relaxed shape of a spiral.

FIG. 21A is a top view of an embodiment of a de-endothelializationdevice including a steering mechanism.

FIG. 21B is a partial cross-sectional top view of thede-endothelialization device of FIG. 21A expanded after being deployedfrom the catheter.

FIG. 22A is a side view of a de-endothelialization device including abasket and being deployed from a delivery catheter.

FIG. 22B is a partial side view of the de-endothelialization device ofFIG. 22A expanded after being deployed from the catheter.

FIG. 23 is a detail of a variation of the de-endothelialization deviceof FIG. 22A, showing the basket rotatably coupled to a core wire.

FIG. 24 is a side view of an alternative embodiment of thede-endothelialization device of FIG. 22A, showing a distal end of thecore wire biased to define an angle with an axis of a proximal portionof the core wire.

FIG. 25A is a partial cross-sectional side view of ade-endothelialization device including a balloon and coupled to a corewire.

FIG. 25B is a partial cross-sectional side view of a variation of thede-endothelialization device of FIG. 25A, showing abrasive elementsforming a pattern at the distal end of the balloon.

FIG. 26 is a side view of a de-endothelialization device.

FIGS. 27 and 28 are partial cross-sectional side views of ade-endothelialization delivery device, including a de-endothelializationdevice having a helical coil shape when disposed and deployed from thedelivery device.

FIG. 29A is a partial cross-sectional side view of ade-endothelialization device electrically coupled to a generator.

FIG. 29B is a partial cross-sectional side view of ade-endothelialization device conductively coupled to a heatable element.

FIG. 30 is a cross-sectional side view of a de-endothelialization deviceincluding an operative element for delivering heat to an endothelium ofan aneurysm.

FIG. 31 is a cross-sectional view of a de-endothelialization fluiddelivery device delivering fluid into an aneurysm.

FIG. 32 is a cross-sectional detail of a variation of thede-endothelialization fluid delivery device of FIG. 31.

FIG. 33A is a cross-sectional detail of another variation of thede-endothelialization fluid delivery device of FIG. 31 including adrainage port.

FIG. 33B is a cross-sectional detail of a variation of thede-endothelialization fluid delivery device of FIG. 33A.

FIG. 33C is a cross-sectional detail of another variation of thede-endothelialization fluid delivery device of FIG. 33A.

FIG. 33D is a cross-sectional detail of yet another variation of thede-endothelialization fluid delivery device of FIG. 33A including aninner tube.

FIG. 34A is a cross-sectional detail of another variation of thede-endothelialization fluid delivery device of FIG. 32 including astopper.

FIG. 34B is a detail of the de-endothelialization fluid delivery deviceof FIG. 34A, showing the stopper in a low profile disposed within asheath.

FIG. 34C is a detail of a variation of the de-endothelialization fluiddelivery device of FIG. 34A including a stopper.

FIG. 34D is a detail of the de-endothelialization fluid delivery deviceof FIG. 34C, showing the stopper compressed into a low profile within asheath.

FIG. 34E is a partial cross-sectional side view of thede-endothelialization fluid delivery device of FIG. 34A, showing thestopper being deployed within an aneurysm.

FIG. 34F is a cross-sectional side view of a variation of thede-endothelialization fluid delivery device of FIG. 34A, showing astopper having an elliptical shape.

FIG. 35 is a partial cross-sectional side view of an alternativeembodiment of a de-endothelialization fluid delivery device.

FIG. 36 is a partial cross-sectional side view of a variation of thede-endothelialization fluid delivery device of FIG. 35.

FIG. 37 is a partial cross-sectional side view of a variation of thede-endothelialization fluid delivery device of FIG. 36.

FIG. 38A is a partial side view of a de-endothelialization fluiddelivery device including a balloon deployed within an aneurysm.

FIG. 38B is a cross section of the de-endothelialization fluid deliverydevice of FIG. 38A.

FIG. 39A is a cross-sectional view of a variation of thede-endothelialization fluid delivery device of FIG. 38A including aballoon having a drainage port.

FIG. 39B is a cross sectional view of the delivery tube of thede-endothelialization fluid delivery device of FIG. 39A taken along line39B-39B.

FIG. 40A is a cross section of a variation of the de-endothelializationfluid delivery device of FIG. 39A including a drainage port coupled to adrainage tube.

FIG. 40B is a cross sectional view of the delivery tube of thede-endothelialization fluid delivery device of FIG. 40A taken along line40B-40B.

FIG. 41 is a cross-sectional view of a variation of thede-endothelialization fluid delivery device of FIG. 38A including astopper.

FIG. 42 is a side view of a de-endothelialization fluid delivery deviceincluding a triple-lumen catheter.

FIG. 42A is a cross-sectional view of another variation of thede-endothelialization fluid delivery device of FIG. 38A, including afluid delivery lumen formed within a wall of the balloon for deliveringde-endothelialization fluid.

FIG. 42B is a cross-sectional view of another variation of thede-endothelialization fluid delivery device of FIG. 38A including aseparate tube coaxially surrounded by the delivery tube.

FIG. 43A is a side view of a de-endothelialization system including aperfusion balloon.

FIG. 43B is a perspective view of a variation of the perfusion balloonof the de-endothelialization system of FIG. 43A.

FIG. 43C is a cross sectional view of the perfusion balloon of FIG. 43Btaken along line 43C-43C.

FIG. 44A is a side view of a de-endothelialization fluid delivery deviceincluding a triple-lumen catheter.

FIG. 44B is a cross sectional view of the triple-lumen catheter of FIG.44A taken along line 44B-44B.

FIG. 44C is a cross-sectional view of a variation of the triple-lumencatheter of FIG. 44A.

FIG. 44D is a cross-sectional view of another variation of thetriple-lumen catheter of FIG. 44A.

FIG. 45 is a side view of a de-endothelialization fluid delivery deviceincluding an expandable applicator deployable from a delivery sheath.

FIG. 46 is a partial cross-sectional view of the de-endothelializationfluid delivery device of FIG. 45, showing the applicator compressed intoa low profile within the sheath.

FIG. 47 is a side view of a de-endothelialization device including afiber attached to an elongate core member.

FIG. 48 is a side view of a variation of the de-endothelializationdevice of FIG. 47.

FIG. 49 is a side view of another variation of the de-endothelializationdevice of FIG. 47.

FIG. 50 is a cross-sectional side view of a de-endothelialization deviceincluding a coating containing a de-endothelializing compound therein.

FIG. 51 is a cross-sectional side view of a de-endothelialization deviceincluding a hydrogel coating on an elongate core member.

FIGS. 52A-52E show a blood vessel with an aneurysm being treated using adual catheter system, in accordance with the present invention.

FIG. 53 is a cross-sectional side view of a dual syringe system forsimultaneously injecting and aspirating fluid, in accordance with thepresent invention.

FIG. 54 shows an arterio-venous malformation being treated using a dualcatheter system, in accordance with the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Systems and methods of de-endothelializing an aneurysm or other bodylumen are described herein. As used in this specification,“de-endothelializing” or “de-endothelialization” refers to the processof disrupting an endothelium of an aneurysm or other body lumen, whichincludes removing, damaging physically, damaging normal biochemicalfunction, or otherwise damaging and/or destroying a part or all of theendothelium of the wall of an aneurysm or other body lumen. The firstpart of the specification discusses systems and methods ofde-endothelializing an aneurysm or other body lumen using mechanicalinstrumentality. The second part of the specification discusses systemsand methods of de-endothelializing an aneurysm or other body lumen usinga thermal treatment. The third part of the specification discussessystems and methods of de-endothelializing an aneurysm or other bodylumen using a fluid.

I. De-Endothelialization Using Mechanical Instrumentality

A. Implantable De-Endothelialization Devices

FIGS. 1-11 show variations of a de-endothelialization device 10. Thede-endothelialization device 10 includes a core member 12 and one ormore abrasive elements 14 coupled to the core member 12. In general, thecore member 12 carries the abrasive element(s) 14, which are adapted fordisrupting an endothelium of an aneurysm. Optionally, thede-endothelialization device 10(1) may include an end cap 18, as shownin FIG. 1, e.g., a rounded and/or substantially blunt distal tip.

FIG. 1 shows a de-endothelialization device 10(1) that has an elongatecore member 12(1) adapted to be implanted within an aneurysm. The coremember 12(1) preferably has a circular cross-sectional shape.Alternatively, the core member 12(1) may have a rectangular, atriangular, or other geometric cross-sections. The core member 12(1) mayeven have an irregular shaped cross-section.

The core member 12(1) is preferably made of biodegradable materials.Biodegradable or absorbable materials suitable for use in thecompositions of the core member 12(1) may include polymers and proteins.Suitable polymers include, for example, polyglycolic acid, polylacticacid, polycaprolactone, polyhydroxybutyrate, polyhydroxyvalerate,polydioxanone, polycarbonates, polyanhydrides, polyhydroxyalkanoates,polyarylates, polysaccharides, polyamino acids, and copolymers thereof.Non-limiting examples of bioabsorbable proteins include collagen,elastin, fibrinogen, fibronectin, vitronectin, laminin and gelatin. Manyof these materials are commercially available. Fibrin-containingcompositions are commercially available, for example, from Baxter.Collagen containing compositions are commercially available, forexample, from Cohesion Technologies, Inc., Palo Alto, Calif.Fibrinogen-containing compositions are described, for example, in U.S.Pat. Nos. 6,168,788 and 5,290,552, the entirety of which is expresslyincorporated by reference herein. As will be readily apparent,absorbable materials can be used alone or in any combination with eachother. The absorbable material may be in the form of a mono-filament or,alternatively, multi-filament strands.

Furthermore, the absorbable materials may be used in combination withadditional components. For example, lubricious materials (e.g.,hydrophilic) materials may be used to coat the member. One or morebioactive materials may also be included in the composition of the coremember 12(1). The term “bioactive” refers to any agent that exhibitseffects in vivo, for example, a thrombotic agent, a therapeutic agent,and the like. Examples of bioactive materials include cytokines;extra-cellular matrix molecules (e.g., collagen); trace metals (e.g.,copper); matrix metalloproteinase inhibitors; and other molecules thatstabilize thrombus formation or inhibit clot lysis (e.g., proteins orfunctional fragments of proteins, including but not limited to FactorXIII, α₂-antiplasmin, plasminogen activator inhibitor-1 (PAI-1) or thelike). Examples of cytokines that may be used alone or in combination inpracticing the present invention include basic fibroblast growth factor(bFGF), platelet derived growth factor (pDGF), vascular endothelialgrowth factor (VEGF), transforming growth factor beta (TGF-β), and thelike. Cytokines, extra-cellular matrix molecules, and thrombusstabilizing molecules are commercially available from several vendorssuch as Genzyme (Framingham, Mass.), Genentech (South San Francisco,Calif.), Amgen (Thousand Oaks, Calif.), R&D Systems, and Immunex(Seattle, Wash.). Additionally, bioactive polypeptides can besynthesized recombinantly as the sequence of many of these molecules arealso available, for example, from the GenBank database. Thus, it isintended that the invention include use of DNA or RNA encoding any ofthe bioactive molecules.

Furthermore, it is intended that molecules having similar biologicalactivity as wild-type or purified cytokines, matrix metalloproteinaseinhibitors, extra-cellular matrix molecules, thrombus-stabilizingproteins (e.g., recombinantly produced or mutants thereof), and nucleicacid encoding these molecules may also be used. The amount andconcentration of the bioactive materials that may be included in thecomposition of the core member 12(1) may vary, depending on the specificapplication, and can be readily determined by one skilled in the art. Itwill be understood that any combination of materials, concentration, ordosage can be used so long as it is not harmful to the subject.

For the compositions of the core member 12(1), it may also be desirableto include one or more radiopaque materials for use in visualizing thevaso-occlusive members 12(1) in situ. Thus, the vaso-occlusive members12(1) may be coated or mixed with radiopaque materials such as metals(e.g. tantalum, gold, tungsten or platinum), barium sulfate, bismuthoxide, bismuth subcarbonate, and the like.

Alternatively, the core member 12(1) may be made of non-biodegradablematerials, such as metals or alloys, for examples, that are in generalmore elastic than the biodegradable materials described previously.Suitable metals and alloys for the wire making up the coil include thePlatinum Group metals, especially platinum, rhodium, palladium, rhenium,as well as tungsten, gold, silver, tantalum, and alloys of these metals.These metals have significant radiopacity and their alloys may betailored to accomplish an appropriate blend of flexibility andstiffness. They are also largely biologically inert. Additional coatingmaterials, such as polymer, or biodegradable materials as discussedpreviously, may be added to the surface of the core member 12(1) toimprove the lubricity, healing properties, or thrombogenic properties ofthe vaso-occlusive device.

The core member 12(1) may also be of any of a wide variety of stainlesssteels if some sacrifice of radiopacity may be tolerated. Very desirablematerials of construction, from a mechanical point of view, arematerials that maintain their shape despite being subjected to highstress. Certain “super-elastic alloys” include nickel/titanium alloys,copper/zinc alloys, or nickel/aluminum alloys. Alloys that may be usedare also described in U.S. Pat. Nos. 3,174,851, 3,351,463, and3,753,700, the entirety of which is expressly incorporated by referenceherein.

Titanium/nickel alloys known as “nitinol” may also be used in the coremember 12(1). These are super-elastic and very sturdy alloys that willtolerate significant flexing without deformation even when used as avery small diameter wire. If nitinol is used in the device, the diameterof the core member 12(1) may be significantly smaller than that of acore member 12(1) that uses the relatively more ductile platinum orplatinum/tungsten alloy as the material of construction.

The core member 12(1) may also be made of radiolucent fibers or polymers(or metallic threads coated with radiolucent or radiopaque fibers) suchas Dacron (polyester), polyglycolic acid, polylactic acid,fluoropolymers (polytetrafluoroethylene), Nylon (polyamide), or evensilk.

The abrasive element(s) 14 may have a sharp edge (such as that of acutting wire or a knife) or a sharp point, for the purpose of cutting,abrading, and/or penetrating an endothelium of an aneurysm. FIG. 2 showsseveral examples of the shape of the abrasive element(s) 14. Theabrasive element 14 can have a shape of a hook (FIG. 2A), a needle (FIG.2B), a fin (FIG. 2C), a saw tooth (FIG. 2D), a multi-branch hook (FIG.2E), or a ninety degree hook (FIG. 2F). The abrasive element(s) 14 canalso include one or more sharp particles, such as diamond dust, that hasno specific geometric shape. It should be noted that the abrasiveelement(s) 14 can also have a customized shape or other shapes as well.The abrasive element(s) 14 can have a wide range of stiffness, so longas the abrasive element(s) 14 is capable of disrupting an endothelium ofan aneurysm. Furthermore, in order to prevent over-thinning of thearterial or aneurysm wall, that can risk punctures of the arterial oraneurysm wall, the abrasive element 14(s) may have an overall depth thatis less than about five microns. Depending on the particularapplication, the abrasive element(s) 14 may also have an overall depththat is more than about five microns.

As a further alternative, the abrasive element 14 may be an abrasivefibrous structure having fibers adapted for disrupting an endothelium ofan aneurysm. The fibrous structure is preferably coupled to the coremember 12 by frictional contact between the fibrous structure and theouter surface of the core member 12. The surface of the core member 12may be textured to improve coupling between the fibrous structure andthe core member 12. The core member 12 may also include one or moretransverse openings along the length of the core member 12, throughwhich strands of the fibrous structure can be wrapped to secure thefibrous structure to the core member 12. Alternatively, the core member12 may also include protrusions along the length of the core member 12,around which strands of the fibrous structure can be wrapped or hookedto secure the fibrous structure to the core member 12. Alternatively, anadhesive, such as ultraviolet-curable adhesives, silicones,cyanoacrylates, and epoxies, may be used to secure the fibrous structureto the core member 12. Furthermore, the fibrous structure may be coupledto the core member 12 by chemical bonding between reactive groups on thefibrous structure and the core member 12, fusing both materials so thatthey melt together, or temporarily melting the surface of the coremember 12 to embed strands of the fibrous structure.

The abrasive element 14 can be made from a variety of materials, such aspolymers, metals, or plastics. Any of the materials discussed previouslyin reference to the core member 12 may also be suitable for the abrasiveelement 14. The abrasive element 14 can be coupled to the core member 12by a polymer, glue, weld, or brazing. Other types of adhesive may alsobe used, depending on the materials from which the abrasive element 14and the core member 12 are made. Alternatively, the abrasive element 14and the core member 12 can be fabricated together as a single unitduring a manufacturing process. For example, the abrasive element 14 canbe created by removing part(s) of the surface of the core member 12. Theabrasive element 14 may also be molded together with the core member 12when the de-endothelialization device 10 is manufactured. It should benoted that the number of abrasive elements 14, and the patterns orconfigurations formed by the abrasive elements 14, on the surface of thecore member 12 may vary. For example, the de-endothelialization device10 can have a single or a plurality of abrasive elements 14.Furthermore, the core member 12 can be completely or partially coveredby the abrasive element(s) 14 in a random or designed pattern.

The de-endothelialization device 10(1) described above generally has asubstantially rectilinear or a curvilinear (slightly curved, i.e. havingless than 360° spiral) relaxed configurations. This configuration may bereferred to as a “primary shape,” i.e., referring to the basic shape ofthe device material. Such a device may assume folded configurations whenthey are subjected to an external force, e.g., buckling or compressiveforces when they encounter objects.

In addition or alternatively, the vaso-occlusive device may include a“secondary relaxed shape,” which may be formed by wrapping a core memberhaving a primary shape that is substantially linear around a shapingelement. The secondary shape may be a helical coil or other shapes.

In addition or as a further alternative, the vaso-occlusive device mayalso assume a “tertiary relaxed shape,” which may be formed, forexample, by wrapping a core member having a primary or secondary shapearound a shaping element. The tertiary shape may be, for example, in ashape of a clover leaf, a twisted figure eight, a flower, a sphere, avortex, an ovoid, or random shapes.

A secondary and/or tertiary shape may be programmed into a device usingknown heat treatment processes or other shape memory materialproperties. Once programmed, the device may be biased to a “relaxedstate” including both a primary shape, secondary, and/or tertiary shape.This relaxed state may also be referred to as a lowest energy state,because, when the device is deformed into any other shape, it may storeelastic energy that is removed as the device returns towards the relaxedstate.

For a device that has a secondary and/or tertiary shape, the core member12 is preferably made from a substantially resilient material, havingsufficient rigidity to support the de-endothelialization device in thesecondary and/or tertiary state when deployed, e.g., within an aneurysmor other body space. Thus, the space-filling capacity of these devicesmay be inherent within the secondary and/or tertiary relaxed shapes ofthese devices.

FIGS. 3 and 4 illustrates de-endothelialization devices 10 havingsecondary shapes. These shapes are simply indicative of the varioussecondary shapes that may be used, and other shapes may be used as well.The device 10 illustrated in each of the FIGS. 3 and 4 includes theabrasive element 14 as described previously, but is not shown forclarity.

FIG. 3 depicts a de-endothelialization device 10(2) having a secondaryshape of a helical coil. The helical coil can have an open pitch, suchas that shown in FIG. 3, or a closed pitch. FIG. 4 illustrates ade-endothelialization device 10(3) having a random secondary shape. Eachof the secondary shapes shown in FIGS. 3 and 4 may be achieved bywrapping a core member 12 having a primary shape that is substantiallylinear, such as that shown in FIG. 1, around a mandrel, stylet, or othershaping element. The device 10 may be subjected to a heat treatment orother step known to those skilled in the art for setting the secondaryshape of the device 10. Forming devices, such as vaso-occlusive devices,into secondary shapes is well known in the art, and need not bedescribed in further detail.

FIGS. 5-11 illustrate various de-endothelialization devices 10 of thisinvention having a secondary shape of a helical coil, such as that shownin FIG. 3, and a tertiary shape. These shapes are simply indicative ofthe various tertiary shapes that may be used, and other shapes may beused as well. While not shown, the devices 10 illustrated in each of theFIGS. 5-11 include the abrasive element 14, as discussed previously.

FIG. 5 depicts a device 10(4) having a tertiary shape of a clover leaf.FIG. 6 depicts a device 10(5) having a tertiary shape of a twistedfigure-8. FIG. 7 depicts a device 10(6) having a flower-shaped tertiaryshape. FIG. 8 depicts a device 10(7) having a substantially sphericaltertiary shape. FIG. 9 illustrates a device 10(8) having a randomtertiary shape. FIG. 10 illustrates a device 10(9) having tertiary shapeof a vortex. FIG. 11 illustrates a device 10(10) having a tertiary shapeof an ovoid. It should be noted that de-endothelialization device 10 mayalso have other secondary and tertiary shapes, and should not be limitedto the examples illustrated previously. For example, the core member 12,and accordingly, the de-endothelialization device, can be selectivelysized to fill a particular aneurysm.

To make the tertiary shaped de-endothelialization devices 10, a coremember 12 that is substantially rectilinear or curvilinear may bewrapped around a mandrel or other shaping element to form a secondaryshape, such as the helical coil shown in FIG. 3. The mandrel and thecore member 12 may be heated to shape the core member 12 into thesecondary shape. The secondary shaped core member 12, or as in the casefor the devices shown in FIGS. 5-11, the helical coil, is then wrappedaround another shaping element to produce the tertiary shape. Heat mayalso be used to shape the core member 12 to form the tertiary shape.Stable coil designs, and methods of making such, are described in U.S.Pat. No. 6,322,576B1 to Wallace et al., the entirety of which isexpressly incorporated by reference herein. It should be noted thatforming devices, such as vaso-occlusive devices, into secondary andtertiary shapes is well known in the art, and need not be described infurther detail.

The method of using the previously described de-endothelializationdevices will now be discussed with reference to FIGS. 12-15. First, adelivery catheter 42 is inserted into the body of a patient, e.g.,percutaneously through a peripheral vessel, such as a femoral, carotid,or radial artery. Other entry sites sometimes are well known tophysicians who practice these types of medical procedures. The deliverycatheter 42, which may be a micro-catheter, sheath, or other elongatedevice, is positioned so that the distal end 48 of the delivery catheter42 is appropriately situated, e.g., within the mouth of the body cavity41 to be treated. The delivery catheter 42 may be advanced over orotherwise in conjunction with a guidewire, guiding catheter, or otherrail, as is known in the art. In addition, the catheter 42 may bemonitored, e.g., using fluoroscopy, during advancement.

Once the delivery catheter 42 is in place, the de-endothelializationdevice 10 may be inserted from the proximal end (not shown) of thedelivery device 42 into a lumen of the delivery catheter 42. If desired,the de-endothelialization device 10 can be heated, e.g., to atemperature above 50° C., or cooled, e.g., to a temperature below 0° C.,to enhance the de-endothelializing property of the de-endothelializationdevice 10. The endothelium of the aneurysm or other body lumen can beinjured or destroyed simply by heating, e.g., to a temperature above 50°C., or cooling, e.g., to a temperature below 0° C., as explained furtherbelow.

For a de-endothelialization device, such as the device 10 shown in FIG.1 having no secondary shape, the de-endothelialization device 10 maynaturally assume its substantially rectilinear or a curvilinear primaryshape when disposed within the lumen of the delivery catheter 42,without being subjected to substantial stress. When thede-endothelialization device 10 is disposed within the lumen of thedelivery catheter 42, the abrasive element(s) 14 may assume a bent orcollapsed configuration. Alternatively, the lumen of the deliverycatheter 42 can be made sufficiently wide to accommodate thede-endothelialization device 10 without substantially bending theabrasive element(s) 14. For de-endothelialization devices havingsecondary and/or tertiary shapes, such as the de-endothelializationdevices shown in FIGS. 3-11, they may be “stretched” or straightened toa substantially linear shape primary or secondary shape while residingwithin the lumen of the delivery catheter 42, as illustrated with thede-endothelialization device 10 in FIG. 13. A de-endothelializationdevice that can assume a linear shape within the delivery device 42 maysubstantially reduce the cross-sectional dimension required of thedelivery catheter 42, which may assist advancing the catheter 42 intothe body of a patient and improves the maneuverability of the catheter42 within the body, e.g., through narrow vessels and/or tortuousanatomy.

Alternatively, as shown in FIG. 14, a de-endothelialization devicehaving a secondary shape of a helical coil, such as thede-endothelialization device 10, may be disposed within the lumen of adelivery catheter in an unstretched configuration. Furthermore, as shownin FIG. 15, a de-endothelialization device having a secondary shape madeof a helical coil, such as the de-endothelialization device 10, may be“stretched” from its tertiary shape into a substantially linear helicalcoil, when disposed within the lumen of a delivery catheter 42.

Referring back to FIG. 12, the de-endothelialization device 10 ispreferably advanced distally towards the distal end 48 of the deliverycatheter 42 using a core wire or pusher member 44. A plunger 46 may beattached to the distal end of the core wire 44 to assist advancing thede-endothelialization device 10. Alternatively, fluid pressure may alsobe used to advance the de-endothelialization device 10 along thedelivery catheter 42. The inner diameter of the delivery catheter 42should be made large enough to allow advancement of thede-endothelialization device 10. On the other hand, the inner diameterof the delivery catheter 42 should not be significantly larger than theoverall cross-sectional dimension of the de-endothelialization device 10in order to avoid bending and kinking of the de-endothelializationdevice 10 within the lumen of the delivery catheter 42.

For a de-endothelialization device having no secondary relaxed shape orhaving a secondary shape that is substantially rectilinear orcurvilinear, such as a substantially linear helical coil, thede-endothelialization device may remain substantially rectilinear orcurvilinear without undergoing substantial stress while disposed withinthe lumen of the delivery catheter 42. Once the de-endothelializationdevice 10 or a portion of the de-endothelialization device 10 exits fromthe distal end 48 of the delivery catheter 42, it may remainsubstantially rectilinear or curvilinear until it contacts an object,e.g., the wall of the body cavity 41. If the de-endothelializationdevice 10 is advanced further distally, i.e., to introduce additionallength into the body cavity, the de-endothelialization device 10 maybuckle and/or bend due to the distal force exerted by the device againstthe object that it contacts. Consequently, the de-endothelializationdevice 10 may fold, thereby forming a three-dimensional structure foroccupying the aneurysm. For de-endothelialization devices havingsecondary and/or tertiary shapes, the de-endothelialization device mayattempt to assume its relaxed secondary and/or tertiary shape whenejected from the lumen of the delivery catheter 42. The shape of thesecondary and/or tertiary shapes may help fill the body cavity 41.

Optionally, one or more additional de-endothelialization devices 10 mayalso be placed within the body cavity 41 by repeating the relevant stepsdiscussed above. When a desired number of de-endothelialization deviceshave been placed within the body cavity 41, the delivery catheter 42 isthen withdrawn from the body cavity 41.

During and/or after placing the de-endothelialization devices 10 in thebody cavity 41, the abrasive element(s) 14 of the de-endothelializationdevice(s) may disrupt the endothelium of the aneurysm, blood vessel, orother body lumen, causing the lumen wall to produce afibro-proliferative reaction. As a result, fibrous tissue containingcollagen may form at the disrupted endothelium, thereby thickening thewall of the aneurysm or body lumen. The thickening of the wall of theaneurysm or body lumen may reduce the risk of rupturing and/or growth ofthe aneurysm, thereby enhancing stabilization of the aneurysm, and/orenhancing stable occlusion of the aneurysm or body lumen. Eventually, anembolism may form to occlude the body cavity 41.

FIG. 16 depicts an embodiment, generally designated 60, having ade-endothelialization device 10 that may be detached from a core wire 44using a mechanical joint 64. The de-endothelialization device 10 may beany one of the devices depicted in FIGS. 1-11 and described above,including one or more abrasive elements 14 (not shown for clarity).Joint 64 has a clasp section 66 that remains attached to the core wire44 when sheath or catheter body 42 is retracted proximally. Joint 64also includes a second clasp section 68 that is carried on the proximalend of the de-endothelialization device 10 and interlocks with claspsection 66 when the assembly is within sheath 42. When the sheath 42 iswithdrawn from about the assembly, the clasp sections are free todisengage, thus detaching the de-endothelialization device 10. Core wire44 may be electrically connected to a source of radiofrequency energy.

The de-endothelialization devices 10 described herein may also benon-detachable or detachable by electrolytic joints or connectors, suchas those described in U.S. Pat. Nos. 5,234,437, 5,250,071, 5,261,916,5,304,195, 5,312,415, and 5,350,397, the entireties of which areexpressly incorporated by reference herein.

FIG. 17 shows an embodiment, generally designated 70, having ade-endothelialization device 10 that may be detached from a core wire 44using a joint 74 susceptible to electrolysis. The de-endothelializationdevice 10 may be any one of the devices depicted in FIGS. 1-11 anddescribed above, including one or more abrasive elements 14 (not shownfor clarity). Such joints are described in detail in U.S. Pat. No.5,423,829, the entirety of which is expressly incorporated by referenceherein. Joint 74 may be made of a metal that, upon application of asuitable voltage to the core wire 44, may erode in the bloodstream,thereby allowing the de-endothelialization device 10 to detach. Thede-endothelialization device 10 may be made of a metal that is more“noble” in the electromotive series than the metal of joint 74. A returnelectrode (not shown) may be supplied to complete the circuit, as iswell know to those skilled in the art. The region of core wire 44proximal to the joint 74 may be insulated to focus the erosion at thejoint 74. An electrically conductive bushing 76 is used to connect thedistal end of core wire 44 to the proximal end of thede-endothelialization device 10.

For a de-endothelialization device 10 that is detachably coupled to thecore wire 44 (such as those illustrated in FIGS. 16 and 17), thede-endothelialization device 10 may be moved, i.e., advanced, retracted,and/or rotated, within the aneurysm or other body lumen by manipulating(i.e., advancing, retracting, and/or rotating) the proximal end of thecore wire 44. Moving the de-endothelialization device 10 within theaneurysm or other body lumen may increase the surface area of theendothelium disrupted by the abrasive element(s) 14 of thede-endothelialization device 10. After the endothelium of the aneurysmor other body lumen has been sufficiently disrupted, thede-endothelialization device 10 may be de-coupled from the core wire 44.If desired, one or more additional de-endothelialization device(s) 10may be inserted into the aneurysm or other body lumen, as discussedpreviously.

Although, the de-endothelialization device 10 described previously isadapted to be implanted in a body cavity, such needs not be the case.After the endothelium of the aneurysm or other body lumen has beendisrupted, the de-endothelialization device 10 may be removed from theaneurysm or other body lumen by retracting the proximal end of the corewire 44, thereby causing the de-endothelialization device 10 to moveback into the lumen of the catheter body 42. As such, thede-endothelialization device 10 may be used as a tool without beingimplanted in a body cavity. Thereafter, one or more vaso-occlusivedevices may be delivered to fill the aneurysm or other body lumen. Ifthe aneurysm or other body lumen is small, the de-endothelialization ofthe aneurysm may cause the wall to thicken enough to occlude theaneurysm or other body lumen without using a vaso-occlusive device.De-endothelialization devices not intended for implantation aredescribed further below.

B. Non-Implantable De-Endothelialization Devices

FIGS. 18-24 show variations of a de-endothelialization device 100 thatis adapted to be removed from an aneurysm or other body lumen after anendothelium of the aneurysm or other body lumen has been disrupted.

FIG. 18 shows a de-endothelialization device 100(1) having a core member102 and one or more abrasive elements 104 coupled to the core member102. The abrasive element(s) 104 may be any of the variations of theabrasive element 14 discussed previously. Any of the materials discussedpreviously with reference to the core member 12 may also be used toconstruct the core member 102. The core member 102 is preferablydetachably coupled to a distal end 112 of an elongate member, such as acore wire or a pusher member 114. Thus, if the core member 102 becomesirretrievable during a procedure, the core member 102 can be decoupledfrom the elongate member 114, and left within the aneurysm or other bodylumen as an implant. Alternatively, the core member 102 may be securedto the distal end 112 of the elongate member 114 by a suitable adhesive,which may depend upon the materials from which the elongate member 114and the core member 102 are made. The core member 102 may also befabricated together with the elongate member 114 as one unit duringmanufacturing. In this case, the core member 102 would include theelongate member 114. A handle 116 may optionally be secured to aproximal end 118 of the elongate member 114.

The core member 102 and/or the distal end 112 of the elongate member 114may assume a substantially linear shape, such as that shown in FIG. 18.Alternatively, the core member 102 may also assume a relaxedconfiguration that has a curvilinear shape, such as a J-shape (FIG. 19),a spiral (FIG. 20), or other designed shapes. In general, any of theshapes discussed previously with reference to FIGS. 1-11 may also beused for the core member 102. Although not required, thede-endothelialization device 100(1) may optionally include a tubularelement 120 (such as a sheath or a catheter) capable of coaxiallysurrounding the core member 102 during a procedure. The core member 102and/or the distal end 112 of the elongate member 114 assumes a lowprofile configuration when disposed within a lumen 122 of the tubularelement 120. If the core member 102 and/or the distal end 112 of theelongate member 114 has a non-linear relaxed configuration, the coremember 102 and/or the distal end 102 may assume its relaxedconfiguration when deployed from the tubular element 120.

Turning to FIG. 21A, optionally, the de-endothelialization device 100may include a steering mechanism 130 for changing the shape of thedistal end 112 of the elongate member 104. The steering mechanism 130can vary. For example, FIG. 21 shows a steering mechanism as disclosedin U.S. application Ser. No. 07/789,260, now U.S. Pat. No. 5,363,861issued Nov. 15, 1994, the entirety of which is expressly incorporated byreference herein. As FIG. 21B shows, the steering mechanism 130 mayinclude a rotating cam wheel 132 within the handle 116, and an externalsteering lever or control (not shown) may rotate the cam wheel 132. Thecam wheel 132 holds the proximal ends of right and left steering wires136 and 138. The steering wires 136 and 138 may extend along theassociated left and right side surfaces of the cam wheel 132 and throughthe guide tube 140. The steering wires 136 and 138 connect to left andright sides of a resilient bendable wire or spring within a distalsection of the elongate member 104. Alternatively, the steering wires136 and 138 may connect to a portion of the core member 102.

As FIG. 21A shows, manipulating the steering lever or control causes thedistal end 112 of the elongate member 104 and/or the core member 102 tobend up or down. By rotating the handle, thereby bending the distal end112 of the elongate member 104, and by manipulating the steering lever,it is possible to maneuver the distal end 112 of the elongate member 104virtually in any direction. The steerable section simplifies thepositioning of the distal end 102, and accordingly, the core member 102of the de-endothelialization device 100.

When using the de-endothelialization device 100, the distal end 112(including the de-endothelialization device 100) of the elongate member104 is first positioned inside an aneurysm or other body lumen.Positioning the distal end 112 of the elongate member 104 may befacilitated using a guide wire and/or sheath (such as the tubularelement 120), as is known to those skilled in the art. If desired, thede-endothelialization device 100 may be heated or cooled to a certaintemperature to enhance the de-endothelializing capability of thede-endothelialization device 100, as discussed previously. Next, bymanipulating (i.e., advancing, retracting, and/or turning) the proximalend 118 of the elongate member 104 (or the handle 116 if one isprovided), the core member 102 of the de-endothelialization device 100may be positioned at various locations against the endothelium of theaneurysm or other body lumen, thereby disrupting the endothelium of thevarious locations of the aneurysm or other body lumen. If a steeringmechanism 130 is provided, the steering mechanism 130 may also be usedto position the core member 102 of the de-endothelialization device 100.

After the abrasive element 104 of the de-endothelialization device 100has disrupted sufficient surface area of the endothelium of the aneurysmor other body lumen, the de-endothelialization device 100 may bewithdrawn from the aneurysm or other body lumen. After some time,fibrous tissue may form at the disrupted endothelium, causing the wallof the aneurysm or other body lumen to thicken, as discussed above withreference to implantable de-endothelialization devices. For an aneurysmor other body lumen having a certain size, it may be desirable todeliver one or more vaso-occlusive device(s) into the aneurysm or otherbody lumen after the de-endothelialization device 100 has been removedfrom the aneurysm or other body lumen. Alternatively, if the aneurysm orother body lumen is small, the de-endothelialization of the aneurysm orother body lumen may cause the wall to thicken enough to occlude theaneurysm or other body lumen without requiring a vaso-occlusive deviceto be implanted.

In certain situations, it may be desirable to disrupt the neck of ananeurysm, with or without de-endothelializing the wall of the aneurysmsac. For example, when the neck of an aneurysm is small,de-endothelializing just the neck may cause the neck of the aneurysm tothicken, thereby closing the neck. For a wide neck aneurysm,de-endothelializing the neck of the aneurysm may have the benefit ofreducing the size of the neck. It should be noted that the embodimentsof de-endothelialization devices described above may also be suitablefor disrupting the neck of an aneurysm, and that the methods describedabove may be used for this purpose.

FIGS. 22-24 show variations of a de-endothelialization device 100,including an expandable member coupled to a core wire or other elongatemember 114. FIG. 22A shows a de-endothelialization device 100(2)including one or more abrasive elements 104, and an expandable basket150. Although the expandable basket 150 is shown to include two flexiblewires 152, it may include any number of wires 152. Furthermore, thebasket 150 is not necessarily limited to the example illustrated in FIG.22. Alternatively, the basket 150 may include a braided structure or amesh. The basket 150 is preferably made of an elastic material, such asnitinol, although other materials may also be used. The distal end ofthe basket 150 may be secured to the elongate member 114 such thatrotating the proximal end 118 of the elongate member 114 may cause theexpandable basket 150 to rotate. Alternatively, as shown in FIG. 23, thedistal end of the expandable basket 150 may be rotatably secured to theelongate member 114 so that the basket 150 can rotate about the elongatemember 114. In either case, the basket 150 may be rotated manually orautomatically, e.g., by a machine.

As shown in FIGS. 22A and 22B, the basket 150 may assume a low orcollapsed profile while disposed within the lumen of the tubular element120, and is free to assume an expanded profile when it is outside thetubular element 120. The basket 150 may be self-expanding orself-collapsing. A self-expanding basket has a relaxed expandedconfiguration, and may be collapsed by directing opposite ends 154 and156 of the wires 152 (or the elements defining the basket 150) furtherfrom one another. A self-collapsing basket has a relaxed collapsed (orunexpanded) configuration, and may be expanded by directing oppositeends 154 and 156 of the wires 152 (or the elements defining the basket150) closer towards one another. The shape of the basket 150 may bechanged, for example, by varying the tension or compression on any orall of the wires 152 via a control (not shown). FIGS. 22A and 22B showthat the elongate member 114 is substantially linear. Alternatively, asshown in FIG. 24, the distal end 112 of the elongate member 114 may bebent or preformed such that it forms an angle 160 with an axis 162 of aproximal portion of the elongate member 114. Expandable baskets that maybe used are described in U.S. Pat. Nos. 5,893,847, 5,925,038, and6,216,044, the disclosures of which are expressly incorporated byreference herein.

FIG. 25A shows a de-endothelialization device 100(3) that includes aplurality of abrasive elements 104 carried by a balloon 170. The balloon170 has a proximal end 171 coupled to a distal end 172 of a core tube174. The core tube 174 also includes a proximal end 176, an opening 177at the proximal end 176, and a lumen 178 (not shown) extending betweenthe distal end 172 and the proximal end 176.

The proximal end 171 of the balloon 170 is preferably detachably coupledto the distal end 172 of the core tube 174 by a joint 180, such as anelectrolytic joint or a mechanical joint, as discussed previously withreference to FIGS. 16 and 17. This may allow the balloon 170 to bede-coupled from the core tube 174 if the balloon 170 cannot be retrievedduring a procedure. The balloon 170 may also be secured to the distalend 172 of the core tube 174 by a glue or other suitable adhesive.Alternatively, the balloon 170 can be fabricated with the core tube 174as one unit during manufacturing. Optionally, the de-endothelializationdevice 100(3) may include the core tube 174. The endothelializationdevice 100(3) may also optionally include a tubular element 182, such asa sheath or a catheter, that is capable of surrounding the core tube 174and the balloon 170 when it is un-inflated.

The balloon 170 is preferably made of thermoplastic or elastomericmaterials, such as polyimide (kapton), polyester, silicone rubber,nylon, mylar, polyethylene, or polyvinyl chloride. However, otherelastic or inelastic materials known in the art may also be used forconstructing the balloon 170. Expandable balloons have been described inU.S. Pat. No. 5,925,083, the entirety of which is expressly incorporatedby reference herein.

It should be noted that the shape of the expandable member (i.e., thebasket 150 or the balloon 170) is not necessarily limited to thoseillustrated in the figures, and other shapes may also be used.Furthermore, various patterns may be formed by the abrasive element(s)104 on the surface of the expandable member so that only a desiredportion of the endothelium of the aneurysm or other body lumen isdisrupted. FIG. 25B shows a balloon 170 wherein only the distal end ofthe balloon 170 is covered by the abrasive elements 104. Other patternsof the abrasive element(s) 104 may also be used.

When using a de-endothelialization device 100 having an expandablemember (i.e., the basket 150 or the balloon 170), the tubular element182 is first positioned so that the distal end of the tubular element182 is adjacent to a neck of an aneurysm or at the site of another bodylumen to be de-endothelialized. The tubular element 182 may be placedusing a guide wire or other rail, as is known in the art. The expandablemember is initially collapsed and placed within the lumen of the tubularelement 182. The expandable member may be inserted into a lumen 184 ofthe tubular element 182 after the distal end of the tubular element 182has been placed adjacent to the neck of the aneurysm or at the site ofanother body lumen to be de-endothelialized. Alternatively, theexpandable member may be inserted into the lumen 184 of the tubularelement 182 first, and the tubular element 182 carrying the expandablemember may then be placed into a vessel leading to the aneurysm or atthe site of another body lumen to be de-endothelialized.

The distal tip of the tubular element 182 is preferably placed withinthe aneurysm or at the site of another body lumen to bede-endothelialized. However, the distal tip of the tubular element 182may also be placed outside the aneurysm adjacent to the neck of theaneurysm so long as the expandable member can be deployed into theaneurysm, or placed adjacent to the segment of vessel to bede-endothelialized so long as the expandable member can be deployed intothe segment of vessel to be de-endothelialized. When the distal tip ofthe tubular element 182 is positioned as desired, the expandable memberis then expanded. For the de-endothelialization device 100 including theballoon 170, the balloon 170 is expanded by delivering a fluid throughthe opening 177 and into the lumen 178 of the core tube 174. The coretube 174 delivers the fluid into an interior of the balloon 170, therebyexpanding the balloon 170. The fluid can be a gas or a liquid, such aswater, saline, or blood. A radio-opaque marker (not shown) may becarried at the distal end of the tubular element 182 and/or theexpandable member to help positioning the tubular element 182 and/or theexpandable member relative to the aneurysm or other body lumen.

If the expandable member has an expanded shape that substantiallyoccupies an aneurysm or other body lumen, the abrasive elements 104 maydisrupt the endothelium of the aneurysm or other body lumen when theexpandable member is expanded. The expandable member may also have anexpanded shape that is slightly larger than the aneurysm or other bodylumen to enhance the de-endothelialization property of thede-endothelialization device 100. After the endothelium of the aneurysmor other body lumen is disrupted, the expandable member is thencollapsed and removed from the aneurysm or other body lumen.

Alternatively, before the expandable member is collapsed, the expandablemember may be moved within the aneurysm or other body lumen bymanipulating the handle 116, thereby causing further disruption to theendothelium of the aneurysm or other body lumen. After the abrasiveelement 104 of the de-endothelialization device 100 has disrupted asufficient area of the endothelium of the aneurysm or other body lumen,the de-endothelialization device 100 may then be withdrawn from theaneurysm or other body lumen.

II. De-Endothelialization Using Thermal Treatment

A. De-Endothelialization Using a Heated or Cooled Implant

The endothelium of an aneurysm can also be disrupted by altering thetemperature of the endothelium. As mentioned previously, the endotheliumof an aneurysm or other body lumen can be injured or destroyed at atemperature that is above 50° C. or below 0° C. FIG. 26 shows an exampleof a de-endothelialization device 200 adapted to be heated or cooled toa de-endothelializing temperature. The de-endothelialization device 200can be a variety of objects, such as a vaso-occlusive device, so long asit is capable of reaching a temperature that is sufficient fordisrupting an endothelium of an aneurysm or other body lumen. Thede-endothelialization device 200 can be thermally treated by placing itin a freezer or in an oven. Alternatively, the de-endothelializationdevice 200 can also be thermally treated by placing it in a media, suchas water or saline, that has been heated or cooled. Other methods knownin the art for altering a temperature of an object can also be used.

The de-endothelialization device 200 can have a variety of shapes orforms. The de-endothelialization device 200 preferably has a relaxed,secondary shape of a helical coil, as shown in FIG. 26. However, any ofthe shapes discussed previously with reference to FIGS. 1-11 is alsoapplicable to the de-endothelialization device 200. In particular, thede-endothelialization device 200 can have a tertiary shape. Thede-endothelialization device 200 can also include an expandable member,such as a balloon or a basket, as discussed previously. Other shapes ofdevices capable of being placed within a body cavity may also be used,as are known in the art.

The de-endothelialization device 200 should be made from a material thatcan maintain its structural integrity in a de-endothelializingtemperature. That is, the de-endothelialization device 200 should bemade from a material such that it will not melt or become too brittlewhen subjected to the desired thermal treatment. In general, because oftheir high thermal conductivity, metals are preferable materials forconstructing the de-endothelialization device 200. Also, any of thematerials discussed previously with reference to the core member 12 ofthe de-endothelialization device 10 can also be used, so long as thede-endothelialization device 200 remains deliverable to an aneurysmafter thermal treatment. Other materials known in the art may also beused for the constructing the de-endothelialization device 200.

FIG. 27 shows a de-endothelialization device 200(1) that is adapted tobe thermally treated before it is delivered to an aneurysm or other bodylumen. A tubular element 210, such as a sheath or a catheter, is used todeliver the vaso-occlusive device 200(1) to an aneurysm or other bodylumen. The tubular element 210 includes an insulative layer 212 at aninterior surface of the tubular element 210. The insulative layer 212prevents or reduces the amount of thermal transfer from thede-endothelialization device 200(1) to an exterior surface 214 of thetubular element 210. The insulative layer 212 is preferably made of apolymer. However, other materials having desired thermal insulationproperties known in the art may also be used. If the tubular element 210is made from a material that possesses desired thermal insulationproperties, then the insulative layer 212 becomes optional, and is notrequired.

FIG. 27 shows that the de-endothelialization device 200 has a secondaryshape of a helical coil when disposed within the lumen of the tubularelement 210. However, as discussed previously, such needs not to be thecase. As shown in FIG. 28, the de-endothelialization device 200(1) canalso be stretched to a substantially linear or curvilinear shape whendisposed within the lumen of the tubular element 210. The method ofdelivering the de-endothelialization device 200(1) is similar to thatdiscussed previously with reference to FIGS. 12-15.

FIG. 29A shows a de-endothelialization device 200(2) that is adapted tobe heated after it has been placed within an aneurysm or other bodylumen. The de-endothelialization device 200(2) may optionally include atubular element 224, such as a sheath or a catheter. Thede-endothelialization device 200(2) is electrically coupled to a corewire 220 that delivers electrical energy from a source of electricalenergy, such as a radio frequency (RF) generator 222, to the device200(2). The de-endothelialization device 200(2) acts as a resistor andconverts the electrical energy to heat. Alternatively, as shown in FIG.29B, the de-endothelialization device 200(2) may be mechanically coupledto a heatable element 223. The heatable element 223 may act as aresistor and convert electrical energy from the generator 222 to heat.Because of the mechanical coupling between the heatable element 223 andthe de-endothelialization device 200(2), heat flows from the heatableelement 223 to the de-endothelialization device 200(2) by conduction.

When using the de-endothelialization device 200(2), thede-endothelialization device 200(2) is first placed within the aneurysmor other body lumen by any conventionally known method. For example, thetubular element 224 may first be inserted into a vasculature of apatient such that the distal end of the tubular element 224 is adjacentto an aneurysm or other body lumen. The de-endothelialization device200(2) can then be delivered to the aneurysm or other body lumen via thetubular element 224.

Once positioned within the aneurysm or other body lumen, thede-endothelialization device 200(2) is then heated. When the temperatureof the de-endothelialization device 200(2) reaches a desired level, thede-endothelialization device 200(2) can then be de-coupled from the corewire 220 by methods that are described previously. The tubular element224 and/or the core wire 220 may optionally include a sensor, such as athermistor, to monitor the temperature at the distal end of the corewire 220.

Although the de-endothelialization device 200(2) is adapted to bedeployed within a body cavity as an implant, such needs not be the case.After the endothelium of the aneurysm or other body lumen has beensufficiently disrupted by the heated de-endothelialization device200(2), the de-endothelialization device 200(2) can be removed from theaneurysm or other body lumen by retracting a proximal end of the corewire 220, thereby causing the de-endothelialization device 200(2) toretract back into the lumen of a tubular element 224. As such, thede-endothelialization device 200(2) may also be used as a tool withoutbeing implanted in a body cavity. One or more vaso-occlusive devices maythen be delivered to fill the aneurysm or other body lumen. If theaneurysm or other body lumen is small, the de-endothelialization of theaneurysm may cause the wall to be thicken enough to occlude the aneurysmwithout using a vaso-occlusive device.

B. De-Endothelialization Using a Heat Delivery Device

FIG. 30 shows a de-endothelialization device 300 that is adapted todeliver heat energy to an endothelium of an aneurysm. Thede-endothelialization device 300 includes an operative element 302 andan elongate member 304 having a distal end 306 and a proximal end 308.The operative element 302 is carried at the distal end 306 of theelongate member 304, and is adapted to be electrically coupled to agenerator 310. Optionally, the de-endothelialization device 300 mayinclude a sheath 312 having a lumen 314 within which the distal end 306of the member 304 may slide. Optionally, the de-endothelializationdevice 300 may also include a steering mechanism, such as that shown inFIGS. 21A and 21B and described above, to facilitate positioning theoperative element 302.

The operative element 302 may have a variety of shapes. In general, anyof the shapes discussed previously with reference to thede-endothelialization devices 10 shown in FIGS. 1-11 may be used for theoperative element 302. The operative element 302 may also include anexpandable basket such as that shown in FIGS. 22-24, in which case eachof the wires 152 (or the elements making up the basket) may beselectively heated. Alternatively, the operative element 302 may includea balloon, such as that shown in FIG. 25A, in which case the balloon maybe heated by supplying and/or circulating heated fluid within theballoon. Cooled fluid may also be used if it is desirable to disrupt theendothelium of an aneurysm or other body lumen using balloon that isbelow a certain temperature.

When using the de-endothelialization device 300, the operative element302 is first inserted into a vein or an artery and positioned within ananeurysm or other body lumen. The sheath 312 and/or a guide wire may beused to facilitate positioning the operative element 302, as is known inthe art. The de-endothelialization device 300 may optionally include aradio-opaque marker on a distal portion of the member 304 and/or thesheath 312, so that the position of the device can be monitored duringthe procedure. The operative element 302 may receive electrical energyfrom the generator 310, and convert the electrical energy generated bythe generator 310 to heat.

The operative element 302 may be used to deliver heat to the endotheliumof an aneurysm or other body lumen by convection or conduction.Delivering heat to the endothelium by convection does not require theoperative element 302 to directly contact the endothelium of theaneurysm or other body lumen. Rather, heat is transferred from theoperative element 302 to the endothelium by the medium, such as blood,that is between the operative element 302 and the endothelium. On theother hand, delivering heat to the endothelium by conduction may requirethe operative element 302 to contact the endothelium of the aneurysm orother body lumen. In either case, the amount of heat generated by theoperative element 302 should be sufficient such that the endothelium ofthe aneurysm or other body lumen is disrupted. The distal end of theelongate member 304 may optionally include a sensor, such as athermistor, to detect a temperature of the operative element 302. Afterthe de-endothelialization process, the operative element 302 of thede-endothelialization device 300 is then removed from the aneurysm orother body lumen.

C. De-Endothelialization Using a Heat Producing or Cooling Chemical

The endothelium of an aneurysm or other body lumen may also be disruptedby a heat producing chemical. For example, a dual lumen catheter may beused to deliver two fluids, such as calcium chloride and water, that,when mixed, undergo a chemical reaction that produces heat.Alternatively, fluids such as ammonium nitrate and water, known to causea cooling reaction when mixed may also be used. U.S. patent applicationSer. No. 10/150,456, the disclosure of which is expressly incorporatedby reference herein, describes a dual lumen catheter that may besuitable for delivering the two heat producing fluids. Othercommercially available dual lumen catheters may also be used.Alternatively, a single lumen catheter may be used to deliver the twofluids, sequentially or alternately, to an aneurysm or other body lumen.

III. De-Endothelialization Using a Fluid

A. Delivery of De-Endothelialization Fluid Using a Fluid Delivery Device

The endothelium of an aneurysm or other body lumen may also be disruptedusing a fluid 350 that is delivered to the endothelium of the aneurysm.As used herein, “fluid” refers to both liquid and gas. The fluid 350 maybe a heated or cooled liquid, such as water or saline. The fluid 350 mayalso contain any cytotoxic agent including, but not limited to oxidizedLDL, perforins, toxin-conjugated antibodies to the endothelial cells,antibodies to the complement protective proteins decay acceleratingfactor (DAF) (also known as CD55), homologous restriction factor (alsoknown as CD59), membrane cofactor protein (MCP) (also known as CD46),mitochondrial inhibitors, inhibitors of cell membrane ion-pumps,hypotonic fluid, hypertonic solution, CD4 T cells, and/or agents thatinduce apoptosis/Fas receptor agonists. Enzymes, such as trypsin orcollagenase, that are capable of chemically removing the endothelialcells from its basement membranes can also be used. The fluid 350 canalso be other drugs, medications, solutions, that are known in the artfor disrupting cells or tissues.

FIG. 31 shows a de-endothelialization fluid delivery device 360(1) thatincludes a delivery tube 362 having a distal end 364, a proximal end366, and a lumen 368 extending between the distal end 364 and theproximal end 366. The delivery tube 362 may be a catheter, microcatheter, or sheath capable of being inserted into a vasculature of amammal. The distal end 364 of the delivery tube 362 is adapted to beplaced adjacent or within an aneurysm or other body lumen, while theproximal end 366 of the delivery tube 362 is adapted to be coupled to afluid source 370. The de-endothelialization fluid delivery device 360may optionally include the fluid source 370. The fluid source 370, whichincludes a container such as a syringe, a bag, a bottle, or anyfluid-holding device, contains the fluid 350 that is capable ofdisrupting an endothelium of an aneurysm or other body lumen, asdiscussed previously.

When using the de-endothelialization fluid delivery device 360, thedistal end 364 of the delivery tube 362 is first placed within theaneurysm or other body lumen. The distal end of the delivery tube 362may optionally include a radio-opaque marker to assist positioning thedelivery tube 362. When the delivery tube 362 is positioned as desired,the fluid 350 is then delivered from the fluid source 370 to within theaneurysm or other body lumen. Optionally, the fluid source 370 mayinclude a pump or syringe for pressurizing the fluid 350 during theprocedure. After the fluid 350 contacts the endothelium of the aneurysmor other body lumen, the de-endothelialization property of the fluid 350causes the endothelium of the aneurysm or other body lumen to bedisrupted. When a desired amount of the fluid 350 has been delivered,the distal end 364 of the delivery tube 362 is then withdrawn from theaneurysm or other body lumen.

In certain situations, it may be desirable to prevent the fluid 350 fromleaving the aneurysm or other body lumen once the fluid 350 has beendelivered into the aneurysm or other body lumen. FIG. 32 shows ade-endothelialization fluid delivery device 360(2) wherein the distalend 364 of the delivery tube 362 has a diameter 380 that issubstantially the same or slightly larger than a diameter of an aneurysmor other body lumen. In this case, after the fluid 350 has beendelivered to the aneurysm, most or all of the excess fluid 350 may flowback into the lumen 368 of the delivery tube 362. Optionally, a sourceof vacuum (not shown) may be coupled to the lumen 368 to aspirate fluidfrom the aneurysm or other body lumen.

FIG. 33A shows another de-endothelialization fluid delivery device360(3) that includes one or more drainage ports 390 at the distal end364 of the delivery tube 362. The delivery tube 362 further includes adrainage lumen 392 that is in fluid communication with the drainageport(s) 390. The de-endothelialization fluid delivery device 360(3) alsohas a distal end diameter 380 that is substantially the same or slightlylarger than a diameter of an aneurysm. The drainage ports 390 arelocated proximal to the distal tip of the delivery tube 362. FIG. 33Bshows a variation of the construction of the delivery tube 362 in whichthe drainage port 390 is also proximal to the distal tip of the deliverytube 362.

When using the de-endothelialization device 360(3), the distal end 364of the delivery tube 362 is inserted into an aneurysm such that thedrainage port(s) 390 is in fluid communication with an interior of theaneurysm. After the fluid 350 has been delivered to the aneurysm throughthe lumen 368 of the delivery tube 362, most or all of the excess fluid350 may flow back into the drainage lumen 392 of the delivery tube 362through the drainage port(s) 390.

FIG. 33A shows that the drainage port 390 is located transversely at awall of the delivery tube 362. However, the drainage port 390 may alsobe located elsewhere. As shown in FIG. 33C, the drainage port 390 mayalso be located at the distal tip of the delivery tube 362. It should benoted that the number of drainage ports 390 may vary. Furthermore, theusage of the lumen 368 of the delivery tube 362 and the lumen 392 mayinterchange. In an alternative embodiment, the lumen 392 may be used todelivery fluid 350 to an aneurysm, and the lumen 368 of the deliverytube 362 may be used to drain or aspirate fluid 350 from the aneurysm.

The previously illustrated embodiments show that the drainage lumen 368is defined within the wall of the delivery tube 362. Alternatively, asshown in FIG. 33D, the delivery tube 362 may include an inner tube 394placed coaxially within the lumen 368 of the delivery tube 362. Theinner tube 394 has a lumen 396 that is in fluid communication with oneor more drainage ports 390 located at the distal end 364 of the deliverytube 362. Excess fluid 350 from the aneurysm may be drained into thedrainage port 390 and delivered to a proximal end via the lumen 396 ofthe inner tube 394. Alternatively, the inner tube 394 may be used todeliver fluid 350 to the aneurysm and the lumen 368 of the delivery tube362 may be used to aspirate excess fluid 350 from the aneurysm to aproximal end of the tube 362.

FIG. 34A shows another de-endothelialization fluid delivery device360(4) that includes the delivery tube 362 and a sealing member orstopper 400 secured to the distal end 364 of the delivery tube 362. Thedevice 360(4) may include one or more drainage ports (not shown) inaccordance with any of the embodiments described above. The stopper 400is used to substantially seal the aneurysm, i.e., to prevent or reducethe risk of having fluid 350 delivered into the aneurysm from escapinginto the artery or vein 402. As such, the diameter 380 of the deliverytube 362 may be substantially the same or smaller than a diameter of theaneurysm, as discussed previously with reference to FIG. 32. If thedelivery tube 362 has a diameter that is substantially the same orslightly larger than a diameter of an aneurysm, then the stopper 400 mayfunction as a back-up device for preventing excess fluid 350 fromflowing into the artery or vein 402. The stopper 400 is preferably madeof a compressible or collapsible material, such as rubber or a foam-likematerial. However, other materials may also be used. The stopper 400should have a shape and dimension such that it may substantially engagetissue around the neck of the aneurysm to substantially seal theaneurysm and prevent substantial leakage of fluid 350 into the artery orvein 402.

The de-endothelialization fluid delivery device 360(4) may optionallyinclude a sheath 404 having a lumen 406. As shown in FIG. 34B, thesheath 404 is capable of surrounding the distal end 364 of the deliverytube 362 such that the stopper 400 assumes a folded configuration whendisposed within the lumen 406 of the sheath 404. Depending on thegeometry of the stopper 400, the stopper 400 may also assume acompressed configuration when disposed within the lumen 406 of thesheath 404 (FIGS. 34C and 34D).

When using the de-endothelialization fluid delivery device 360(4), thesheath 404 is first inserted into an artery or vein and advanced untilthe distal end of the sheath 404 is adjacent an aneurysm. The sheath 404may be advanced over a guide wire or other rail, as is known in the art.The delivery tube 362 may be placed initially within the lumen 406 ofthe sheath 404 and the sheath 404 together with the delivery tube 362may then be positioned adjacent the aneurysm. Alternatively, thedelivery tube 362 may be inserted into the lumen 406 of the sheath 404after the sheath 404 is desirably placed. The stopper 400 may assume abent and/or compressed configuration when disposed within the lumen 406of the sheath 404.

The stopper 400 may be deployed, e.g., by retracting the sheath 404relative to the tubular element 362, or by advancing the delivery tube362 relative to the sheath 404. As shown in FIG. 34A, the stopper 400may be deployed directly outside the neck of the aneurysm such that adistal side 412 of the stopper 400 engages with a vessel wall 413directly outside the aneurysm so that the neck of the aneurysm issubstantially sealed by the stopper 400. Alternatively, as shown in FIG.34E, the stopper 400 can be deployed inside the neck of the aneurysmsuch that the proximal side 410 of the stopper 400 engages with theendothelium of the aneurysm.

The fluid 350 is then delivered to the aneurysm from the fluid supply310. After the fluid 350 contacts the endothelium of the aneurysm, thede-endothelialization property of the fluid 350 causes the endotheliumof the aneurysm to be disrupted. The neck of the aneurysm issubstantially sealed by the stopper 400 during the process such thatfluid 350 may be drained or aspirated via a drainage port 390 withoutsubstantial leaking from the aneurysm into the artery or vein 402. Aftera desired amount of the fluid 350 has been delivered and/or aspirated,the delivery tube 362 and the stopper 400 are then withdrawn back intothe lumen 406 of the sheath 404.

The shape of the stopper 400 should not be limited to the examples shownpreviously and that the stopper 400 may have other shapes. FIG. 34Fshows a de-endothelialization fluid delivery device 360(5) that includesa stopper 400 having an elliptical shape. When using thede-endothelialization fluid delivery device 360(5), a portion of thestopper 400 may be inserted into the aneurysm until the stopper 400bears against a surface 410 that defines the neck of the aneurysm. Ifdesired, the distal end 364 of the delivery tube 362 may be advanced arelatively small increment to compress the stopper 400 within the neckof the aneurysm. This has the benefit of ensuring that the neck of theaneurysm is substantially sealed by the stopper 400. The fluid 350 isthen delivered into the aneurysm, as discussed previously. Fluid 350delivered to the aneurysm may be aspirated or otherwise drained into adrainage port (now shown), the stopper 400 substantially preventing thefluid 350 from leaking from the aneurysm, as discussed previously.

FIG. 35 shows a de-endothelialization fluid delivery device 414 inaccordance with another embodiment of the present invention. Thede-endothelialization fluid delivery device 414 includes an outertubular element 415 and an inner tubular element 416 slidable within alumen of the outer tubular element 415. The outer tubular element 415,which is preferably a micro-catheter or a sheath, may have a diameterthat is the same or slightly larger than the neck of an aneurysm, asdiscussed previously with reference to FIG. 32. The proximal end of theinner tubular element 416 may be coupled to a source ofde-endothelialization fluid (not shown).

When using the de-endothelialization fluid delivery device 414, thedistal tip of the outer tubular element 415 is first placed within theneck of an aneurysm or other body lumen, as shown in FIG. 35. The outertubular element 415 may be placed and/or positioned using similarmethods to those discussed previously, e.g., with reference to FIG. 32,or by conventionally known techniques. The inner tubular element 416 maybe disposed within the lumen of the outer tubular element 415 anddelivered together with the outer tubular element 415 to a target site.Alternatively, the inner tubular element 416 may be inserted into thelumen of the outer tubular element 415 after the outer tubular element415 is desirably situated, and then advanced distally until it reachesthe distal end of the outer tubular element 415. Either or both of theouter and inner tubular elements may include one or more radio-opaquemarkers (not shown) at their respective distal ends for facilitatingpositioning the tubular elements.

When both the outer and inner tubular elements 415 and 416 are desirablepositioned, de-endothelialization fluid is then delivered into theaneurysm or other body lumen via the inner tubular element 416.Depending upon the size and geometry of the aneurysm or other bodylumen, the inner tubular element 416 may be advanced and/or retractedrelative to the outer tubular element 415 at various positions duringand/or before delivering the de-endothelialization fluid. Excessde-endothelialization fluid may be aspirated or drained by the outertubular element 415 during and/or after the delivery of thede-endothelialization fluid. After a desired amount ofde-endothelialization has been delivered, the outer and inner tubularelements 415 and 416 are then withdrawn from the target site.

The de-endothelialization fluid delivery device 414 may further includea coil 417 secured to the distal end of the inner tubular element 416,such as that shown in FIG. 36, to disperse the injected fluid within theaneurysm or other body lumen. The coil 417 is not limited to the linearshape shown in the illustrated embodiment, and may have other shapes aswell. In particular, the coil 417 may have any of the secondary shapesdiscussed previously with reference to FIGS. 5-11. The coil 417 ispreferably made from a radio-opaque material, such as platinum. However,other materials such as stainless steel, aluminum, and/or plastic, mayalso be suitable for constructing the coil 417. Generally, any of thematerials discussed previously with reference to the core member 12 mayalso be used. The length of the coil 417 is preferably from about twomillimeters (2 mm) to about three hundred millimeters (300 mm). The coil417 may also have other lengths, depending on the particularapplication. The spacing between the windings of the coil 417 may vary.Generally, smaller spacing between the windings may better disperse thede-endothelialization fluid.

In the illustrated embodiment, the coil 417 is secured to the distal endof the inner tubular element 416 by an epoxy 418. Other suitableadhesives may also be used. As shown in FIG. 36, the proximal end of thecoil 417 fits around the distal end of the inner tubular element 416.Alternatively, the proximal tip of the coil 417 may abut and be securedto the distal tip of the inner tubular element 416, as shown in FIG. 37.The de-endothelialization fluid delivery device 414 may further includean atraumatic tip 419 secured to the distal end of the coil 417.

When using the de-endothelialization fluid delivery device 414 of FIG.36 in an aneurysm, the distal end of the outer tubular element 415 isfirst placed within the neck of then aneurysm, as discussed previously,e.g., with reference to FIG. 35. The inner tubular element 416 is thenadvanced within the lumen of the outer tubular element 415 until thecoil 417 extends at least partially beyond the distal end of the outertubular element 415 and into the aneurysm. If the coil 417 has asecondary shape or configuration, it may attempt to return towards thesecondary shape as it is deployed from the lumen of the outer tubularelement 415. De-endothelialization fluid may then be delivered via theinner tubular element 416 into the lumen of the coil 417, where it mayescape through spaces between the windings of the coil 417. The windingsof the coil 417 may disperse the de-endothelialization fluid within theaneurysm. De-endothelialization fluid may then be aspirated or drainedby the outer tubular element 415. When a desired amount of thede-endothelialization fluid has been delivered and/or aspirated, theouter and inner tubular elements 415 and 416 may then be withdrawn fromthe treatment site.

It should be understood by those skilled in the art that the outertubular element 415 discussed previously with reference to FIGS. 35-37is primarily used to aspirate excess delivered de-endothelializationfluid, and that, optionally, it may be eliminated (or if provided, itmay not necessarily be placed within the neck of the aneurysm) if thede-endothelialization fluid may be mixed safely with blood. In thiscase, the de-endothelialization fluid may leak out of the sac of theaneurysm without being aspirated or drained by the outer tubular element415.

FIG. 38A shows a de-endothelialization fluid delivery device 420 thatincludes a balloon 422 having a lumen 424 (shown in FIG. 38B), adelivery tube 426, and a sheath 428. The sheath 428 preferably has adiameter or cross-sectional dimension that is the same or slightlylarger than that of a neck of an aneurysm so that it can be used toaspirate de-endothelialization fluid from the aneurysm, as discussedpreviously with reference to the outer tubular element 415 in FIGS.35-37. The balloon 422 is preferably made of a compliant material, suchas silicone, rubber, low density polyethylene, high densitypolyethylene, polypropylene, polybutene, interpolymers or mixtures ofthese polymers, so that when it is inflated, it may conform to the shapeof an aneurysm. In general, any of the materials discussed previouslywith reference to the balloon 170 of FIG. 25A is also applicable forconstructing the balloon 422. The balloon 422 is not limited to theshape shown in the illustrated embodiment, and may have other shapes aswell.

The delivery tube 426 includes a distal end 430, a proximal end 432 (notshown), and a lumen 434 (FIG. 38B) extending between the distal end 430and the proximal end 432. The distal end 430 of the delivery tube 426 iscoupled to the balloon 422 such that the lumen 424 of the balloon 422communicates with the lumen 434 of the delivery tube 426. The balloon422 includes one or more openings 436 that communicate with the lumen424 of the balloon 422. The opening 436 has a size such that, when theballoon 422 is inflated by fluid, the opening 436 may expandsufficiently to allow fluid to exit the balloon 422.

As shown in FIG. 39A, the de-endothelialization device 420 may furtherinclude one or more drainage ports 440 located at a surface of theballoon 422, through which fluid 350 may be aspirated and delivered backto a proximal end (not shown) of the delivery tube 426 via a drainagelumen 442. FIG. 39B is a cross sectional view of the delivery tube 426,showing the drainage lumen 442 inside a wall of the delivery tube 426.FIGS. 40A and 40B show a variation of the de-endothelialization fluiddelivery device 420 in which the drainage lumen 442 is a separatedrainage tube 448 surrounded by the delivery tube 428. It should benoted that the location and number of drainage ports 440 and the shapeof the balloon may vary, and that they should not be limited to theexamples shown in the illustrated embodiments.

FIG. 41 shows another variation of the de-endothelialization fluiddelivery device 420 that includes a sealing member or stopper 450secured to the balloon 422. Although the illustrated embodiment showsthat the stopper 450 extends above the surface of the balloon 422, thestopper 450 may also be constructed such that it is flush with thesurface of the balloon 422. The stopper 450 may have a variety ofshapes, and is not limited to the planar configuration shown in theillustrated embodiment. Furthermore, the stopper 450 may be secured tothe distal end of the delivery tube 428 (not shown, see FIG. 38A)instead of to the balloon 422 so long as the stopper 450 is capable ofsealing the neck of the aneurysm to prevent fluid 350 from leaving theaneurysm. In general, any of the materials discussed previously withreference to the stopper 400 may be used for the stopper 450.

When using the de-endothelialization fluid delivery device 420, theballoon 422 is inflated within the aneurysm by delivering fluid 350 viathe delivery tube 426 into the lumen 424 of the balloon 422. When theballoon 422 is inflated to a certain size, the fluid 350 exits throughthe opening(s) 436 of the balloon 422 due to internal pressure withinthe balloon 422 and/or the size of the opening(s) 436 increasing as theballoon 422 expands. The fluid 350 then contacts the endothelium of theaneurysm, thereby disrupting the endothelium. If thede-endothelialization fluid delivery device 420 includes a drainage port440, it may be used to aspirate fluid 350 from within the aneurysm.Alternatively, if the de-endothelialization fluid delivery device 420includes a stopper 450, the stopper 450 may be used to absorb fluid 350within the aneurysm. When the de-endothelialization process is complete,the balloon 422 may be deflated and removed from the aneurysm.

FIG. 42A shows another variation of the de-endothelialization fluiddelivery device 420 that includes a separate delivery lumen 460 fordelivering fluid to an aneurysm. In this case, the delivery tube 426(not shown, see FIG. 38A) may be used to deliver an inflation fluid,such as water, saline, blood, and/or de-endothelialization fluid 350 tothe lumen 424 of the balloon 422 to inflate the balloon 422. After theballoon 422 has been inflated to a desired size, thede-endothelialization fluid may be delivered via the delivery lumen 460to the aneurysm. FIG. 42A shows that the delivery lumen 460 is formedwithin a wall of the delivery tube 428. Alternatively, as shown in FIG.42B, a separate tube 462 may provide the delivery lumen 460. The tube462 is coaxially surrounded by the delivery tube 428. In either case,the de-endothelialization device 420 may optionally include a drainageport 440 or a stopper 450 as discussed previously.

Optionally, any of the de-endothelialization fluid delivery devicesdescribed previously with reference to FIGS. 31-42B may be used with aperfusion balloon 600, such as that shown in FIG. 43A. The perfusionballoon 600 has a lumen 602, and is coupled to an inflation tube 604such that the lumen 602 of the perfusion balloon 600 is in fluidcommunication with a lumen of the inflation tube 604. The perfusionballoon 600 has a shape such that when it is inflated, it defines anopening 608 for allowing blood to flow through the perfusion balloon600. The perfusion balloon 600 is preferably made of an elasticmaterial, such as a polymer. In general, any of the materials discussedpreviously with reference to the balloon 170 of FIG. 25A may also beused. However, other materials may also be used.

Before using the perfusion balloon 600, a de-endothelialization fluiddelivery device 609 is first placed adjacent or within an aneurysm. Thede-endothelialization fluid delivery device 609 is representative of anyof the de-endothelialization fluid delivery devices described previouslywith reference to FIGS. 31-42B. When using the perfusion balloon 600,the perfusion balloon 600 is delivered to a site where the aneurysm islocated. A sheath 610 may be used to deliver the perfusion balloon 600.If the de-endothelialization device 609 includes a sheath, the sheath ofthe de-endothelialization device may also be used instead to deliver theperfusion balloon 600. The perfusion balloon 600 is collapsed andassumes a low profile when disposed within the lumen of the sheath.

Once the sheath 610 is adjacent the aneurysm, the perfusion balloon 600is deployed from the distal end of the sheath, either by distallyadvancing the perfusion balloon 600 relative to the distal end of thesheath 610, or by retracting the sheath 610 relative to the perfusionballoon 600. An inflation fluid, such as saline, water, blood, or gas isthen delivered by the inflation tube 604 to within the lumen 602 of theperfusion balloon 600, thereby expanding the perfusion balloon 600 untila surface 612 of the perfusion balloon 600 engages the vessel wall 614.As shown in FIG. 43A, when the perfusion balloon 600 is inflated, itforms a barrier substantially sealing the neck of the aneurysm, therebyreducing the chance that fluid 350 delivered into the aneurysm mayescape into the vessel or artery.

FIG. 43B shows a variation of the perfusion balloon 600 that includes aslot 620 in which a portion of the de-endothelialization fluid deliverydevice 609 may be placed. The slot 620 preferably has a depth 622 thatis substantially the same as a diameter of the de-endothelializationfluid delivery device 609. This may allow the de-endothelializationfluid delivery device 609 to form a substantially continuous surfacewith the perfusion balloon 600 to better engage the wall 614 of thevessel or artery, as shown in FIG. 43C.

FIG. 44A shows a de-endothelialization fluid delivery device 640 thatincludes a balloon 642 and a triple-lumen catheter 644. The balloon 642is coupled to a distal portion 646 of the triple-lumen catheter 644. Asshown in FIG. 44B, the triple-lumen catheter 644 includes a first lumen648 that communicates with a lumen 650 of the balloon 642, a secondlumen 652 for delivering de-endothelialization fluid 350 to an aneurysm,and a third lumen 654 for aspirating fluid 350 from the aneurysm. Itshould be noted that the association of specific lumens with respectivepurposes is merely a matter of design choice, and that any of the lumens648, 652, and 654 may be used for inflating the balloon 642, deliveringfluid 350, and draining fluid. The balloon 642 includes one or moreopenings 658 communicating with the second lumen 652 of the triple-lumencatheter 644, and one or more drainage ports 660 communicating with thethird lumen 654 of the triple-lumen catheter 644. The balloon 642preferably has a tubular shape, e.g., similar to the perfusion balloon600 discussed previously, such that blood may continue to flow throughthe vein or artery while the fluid 350 is being delivered to theaneurysm. The de-endothelialization fluid delivery device 640 mayfurther include a sheath 661.

The triple-lumen catheter 644 is not necessarily limited to theconfiguration described previously. FIG. 44C shows a variation of thetriple-lumen catheter 644 that includes a first tube 662 defining thefirst lumen 648, a second tube 664 defining a second lumen 652, and athird tube 666 defining a third lumen 654. The first tube 662 coaxiallysurrounds the second tube 664 and the third tube 666. FIG. 44D showsanother variation of the triple-lumen catheter 644 in which the firsttube 662 surrounds the second tube 664, and the second tube 664, inturn, surrounds the third tube 666.

When using the de-endothelialization fluid delivery device 640, theballoon 642 is first placed adjacent to a neck of the aneurysm. Theballoon 642 may be delivered using a sheath 661 and/or a guide wire, asis known in the art. For example, the sheath 661 may be advanced over aguide wire (not shown) through a vasculature until the distal end of thesheath 661 is adjacent to the neck of the aneurysm. The balloon 642coupled to the triple-lumen catheter 644 may then be deployed from thelumen of the sheath 661, e.g., by advancing the balloon 642 into thelumen from the proximal end of the sheath 661 until it emerges at thedistal end of the sheath 661.

Before and/or after the balloon 642 exits the lumen of the sheath 661,if required, the position and/or the orientation of the balloon may beadjusted by advancing, retracting, and/or rotating the proximal end ofthe triple-lumen catheter 644, until the openings 658 and 660 of theballoon 642 face the opening of the aneurysm. The balloon 642 is theninflated by a media, such as saline, a gas, or other fluid. The balloon642 substantially closes the neck opening of the aneurysm while allowingblood to flow through the vein or artery. Next, de-endothelializationfluid 350 may be delivered through the second lumen 652 of thetriple-lumen catheter 644 into the aneurysm. If thede-endothelialization fluid delivery device 640 includes a drainage port660, fluid 350 may be aspirated from the aneurysm via then port 660.After a desired amount of the fluid 350 has been delivered, the balloon642 is then deflated and withdrawn into the lumen of the sheath 661.

FIG. 45 shows another de-endothelialization fluid delivery device 690that includes an applicator 692, a tube 694, and a sheath 695. Theapplicator is coupled to a distal end 696 of the tube 694, and iscapable of being compressed into a low profile when disposed within thelumen of the sheath 695 (FIG. 46). The applicator 692 is made of aporous and/or absorptive material, e.g., similar to a sponge. The tube694 also has a proximal end 698 that is coupled to the fluid source 370.When using the de-endothelialization device 690, the applicator 692 isfirst deployed into an aneurysm. De-endothelialization fluid 350 is thendelivered via the tube 694 to the applicator 692. Alternatively, theapplicator 692 may also be deployed into the aneurysm after the fluid350 is delivered to the applicator 692. The applicator 692 controls theamount of fluid 350 that may be delivered to the aneurysm, therebyreducing the risk of having excess fluid 350 flowing from the aneurysmto an artery or vessel. It should be noted that applicator 692 may haveother shapes and/or that other types of applicators known in the art mayalso be used.

Turning to FIGS. 52A-52E, a system 810 is shown for treating an aneurysm90 extending from a body lumen, such as a cerebral artery or other bloodvessel 92. Generally, the system 810 includes an outer tubular member812 including a proximal end (not shown), a distal end 814 having a sizeand shape for insertion into the aneurysm 90, and a lumen 816 extendingbetween the proximal end and distal end 814. The system 10 also includesan inner tubular member 822 disposed within the outer tubular member 812that also includes a lumen 826. The inner tubular member 822 may beslidable relative to the outer tubular member 812, e.g., to retract orexpose a distal end 824 of the inner tubular member 822, as will beappreciated by those skilled in the art.

The inner tubular member 822 is substantially smaller than the outertubular member 812 such that the lumen 816 between the inner and outertubular members 822, 812 has a generally annular cross-section. Thelumen 826 within the inner tubular member 822 may be coupled to a sourceof fluid (not shown), thereby providing an infusion lumen, while theannular lumen 816 may be coupled to a source of vacuum (also not shown),thereby providing an aspiration lumen. Alternatively, the functions ofthese lumens 816, 826 may be reversed or they may coupled to othercomponents, as will be appreciated by those skilled in the art.

Turning to FIG. 53, a dual syringe apparatus 850 is shown that may becoupled to the inner and/or outer tubular members 822, 812 shown inFIGS. 52A-52E, e.g., by tubing 818, 828. Generally, the apparatus 850includes first and second syringe barrels 852, 862 including first andsecond chambers 854, 864 and first and second pistons 856, 866,respectively. The barrels 852, 862 may have similar cross-sections ordifferent cross-sections, depending upon whether the delivery andaspiration should be the same or different from one another. The firstand second pistons 856, 866 are movable within the first and secondchambers, respectively, for delivering fluid and/or for aspiratingfluid, as explained further below. In addition, the first barrel 852includes an outlet port 858 and the second barrel 862 has an inlet port868 to which tubing 828, 818 may be connected using conventionalmethods, e.g., luer lock connectors and the like (not shown).

The system 850 also includes an actuator 870 for moving the first piston856, e.g., to deliver fluid within the first chamber 854, and/or formoving the second piston 866, e.g., to aspirate fluid into the secondchamber 864. In the preferred embodiment shown, the actuator 870includes a motor 872 with an output shaft 874 that is coupled to shafts876, 886, e.g., via sprockets or wheels 878, 888. Preferably, the wheels878, 888 are coupled to one another such that, when the motor 872 isoperated, the output shaft 874 simultaneously rotates the wheels 878,888, thereby simultaneously advancing and retracting the pistons 856,866, respectively. It will be appreciated that other actuators may alsobe provided that may be operated manually and/or automatically, insteadof the motor and shaft arrangement shown in FIG. 53. In addition, thevolumetric rates of fluid delivery and fluid aspiration need not be thesame.

It will be appreciated that other fluid moving elements may be providedin addition to or instead of the dual syringes described above. Forexample a fluid delivery pump and as aspiration pump may be coupled tothe delivery and aspiration lumens and to an actuator for simultaneouslydelivering and aspirating fluid, as described elsewhere herein.

Returning to FIGS. 52A-52E, optionally, the system 810 may include anocclusion member 830 for substantially sealing the aneurysm 90 from thevessel 92. In the embodiment shown, the occlusion member 830 includes anexpandable member 832 carried on a distal end 834 of an elongate member836. In a preferred embodiment, the expandable member 832 is acompliant, nonporous balloon and the elongate member 836 is a catheteror micro-catheter including an inflation lumen for infusing fluid intoand/or aspirating fluid from the balloon. Alternatively, a mechanicallyexpandable member (not shown) or other sealing member may be provided.In a further alternative, an expandable member (not shown) may beprovided proximate to the distal end of the outer tubular member 812,rather than on a separate member.

In other alternatives, similar to the embodiment described above, theinner member may be eliminated, and the outer tubular member may includetwo lumens, one for infusion and one for aspiration (not shown). Thelumens may be arranged coaxially, side-by-side, or in any otherconfiguration. The distal end of the outer tubular member may includeone or more ports spaced apart from one another in a desiredarrangement, with one or more ports communicating with respectivelumens.

In yet another alternative, the expandable member may include one ormore ports, and the elongate member may include one or more additionallumens communicating with respective ports, e.g., for infusing oraspirating fluid, similar to the embodiments described above withreference to FIG. 44A. This may allow the inner tubular member to beeliminated, while only requiring the outer tubular member to include onelumen, or may even allow both tubular members to be eliminated.

Returning to FIGS. 52A-52E, a method is shown for treating amalformation, such as an aneurysm 90, extending from a body lumen, suchas a blood vessel 92. Initially, the outer tubular member 812 may beintroduced into the patient's vasculature, e.g., from a percutaneousentry site, and advanced over a guidewire (not shown) until the distalend 814 is located within the aneurysm 90. The outer tubular member 812may include a substantially rounded and/or atraumatic tip to facilitateadvancing the outer tubular member 812 through tortuous anatomy, as iswell known in the art.

The occlusion member 830 may be advanced into the vessel 92 until theexpandable member 832 is disposed adjacent the aneurysm 90. Theocclusion member 830 may be delivered within a catheter, sheath, orother device, e.g., to protect the expandable member 832 and/or thepatient. Once the expandable member 832 is properly positioned, it maybe expanded to substantially seal the aneurysm 90 from the vessel 92, asshown in FIG. 52A. Preferably, the expandable member 832 substantiallyengages the outer tubular member 812, e.g., to enhance the seal againstthe vessel 92 and/or to prevent axial movement of the outer tubularmember 812 relative to the aneurysm 90.

Material, such as blood, other fluid, and/or particulate, may beaspirated from aneurysm, e.g., to substantially clear the interior ofthe aneurysm 90. Preferably, as shown in FIG. 52B, heparinized saline orother isotonic solution with or without a contrast agent is delivered,e.g., via the lumen 826 within the inner tubular member 822, into theaneurysm 90 to facilitate clearing the interior of the aneurysm 90. Morepreferably, the saline or other solution is infused into the aneurysm 90substantially simultaneously with aspirating excess fluid, e.g., saline,solution, blood, and/or loose particulate, from the aneurysm 90, e.g.,using an actuator such as the system 850 shown in FIG. 53.

Because of the occlusion member 830, the fluid being infused into and/oraspirated from the aneurysm 90 without leaking substantially into thevessel 92. In alternative embodiment, the occlusion member 830 may notbe expanded to substantially seal the aneurysm 90 during the infusionand/or aspiration of fluid to clear the aneurysm, e.g., if the fluid issubstantially harmless if it travels downstream in the vessel 92.

Turning to FIG. 52C, a therapeutic fluid may then be delivered into theaneurysm 90. The therapeutic fluid may be intended to cause a variety ofreactions within the aneurysm 90, e.g., cellular lysis, disruption ofcellular adhesions, and/or disruption of cellular function. For example,the therapeutic fluid may include distilled water, a hypo-osmoticsolution, a hyper-osmotic solution, a detergent, a membrane disruptivepolymer solution, and/or a membrane disruptive protein solution capableof causing cellular lysis within the wall of the aneurysm 90.

In addition or alternatively, the therapeutic agent may include asolution capable of disrupting intercellular adhesions, such asproteolytic enzymes (e.g., trypsin), or other agents that disruptadhesive connections between cells. In a further alternative, thetherapeutic fluid may include a solution capable of disrupting orceasing one or more cellular functions, such as ethanol, achemotherapeutic agent, a cytostatic agent, and/or a cytotoxic agent.Optionally, the therapeutic agent may include x-ray contrast, e.g., toidentify when at least some therapeutic agent remains within theaneurysm 90.

As shown in FIG. 52D, once the therapeutic agent has had an opportunityto act within the aneurysm, the therapeutic fluid may be aspirated fromthe aneurysm. Preferably, fluid, such as saline or other isotonicsolution with or without a contrast agent, is infused into the aneurysm90 substantially simultaneously with aspirating excess fluid includingthe therapeutic fluid from the aneurysm. Alternatively, sufficientvacuum may be maintained such that the expandable member 852 may be atleast partially collapsed, thereby allowing fluid from the vessel 92 toenter the aneurysm 90 and fill the void as fluid is aspirated.

Finally, as shown in FIG. 52E, once the therapeutic agent has beensubstantially removed from the aneurysm 90, the expandable member 832may be collapsed, e.g., by aspirating the fluid infused into theexpandable member 832. The outer tubular member 812, inner tubularmember 822, and/or the occlusion member 850 may then be removed from thevessel 92 and from the patient's body, e.g., using conventionalprocedures.

Turning to FIG. 54, a similar method is shown for treating anarterio-venous malformation 94 that extends between an artery 96 and avein 98. Unlike the previous embodiment, separate balloon catheters 860,870 may be introduced into the artery 96 and the vein 98 usingconventional methods. Once positioned as desired, balloons 862, 872 onthe catheters 860, 870 may be expanded to engage the artery 96 and vein98, respectively, thereby substantially isolating the malformation 94from the artery 96 and vein 98.

Fluid within the malformation 94 may be aspirated, e.g., using thecatheter 870 either alone or in conjunction with infusion of saline andthe like, e.g., using the catheter 860. Thus, one catheter may be usedfor infusion while the other is used for aspiration. Optionally, thesystem 850 shown in FIG. 53 or other actuator may be used to infuse andaspirate substantially simultaneously, as described above. Once themalformation is sufficiently cleared, a therapeutic agent, similar tothose described above, may be introduced, e.g., from one or bothcatheters. Optionally, excess fluid may be aspirated from themalformation 94 either during or after the therapeutic agent isintroduced, similar to the method described above. Once the therapeuticagent has remained within the malformation 94 for sufficient time, thetherapeutic agent may be aspirated, e.g., in conjunction with fluidinfusion, similar to the previous embodiments. The balloons 862, 872 maybe collapsed and the catheter 860, 870 removed from the artery 96 andvein 98.

Alternatively, a similar method may be used for introducing ade-endothelialization agent into other blood vessels. For example, aballoon catheter, similar to those described above may be introducedinto a blood vessel adjacent a target treatment site within a bloodvessel, e.g., from a retrograde approach (not shown). A balloon or otherocclusion member may be expanded to engage the wall of the vessel, and atherapeutic fluid may be introduced via the catheter into the targetside, e.g., distal to or upstream from the balloon. The fluid may atleast partially de-endothelialize the vessel wall, e.g., to causefibrous growth that may strengthen the vessel wall and/or may occludethe vessel at the treatment site.

B. Delivery of De-Endothelialization Fluid Using an Implantable Device

De-endothelialization fluid 350 may also be delivered to an aneurysm orother body lumen using an implantable device, such as a vaso-occlusivedevice. FIG. 47 shows a de-endothelialization device 700 that may beused to deliver a de-endothelialization fluid or composition to ananeurysm or other body lumen. The de-endothelialization device 700includes a core member 702 and a fiber 704 secured to the core member702. The fiber 704 is capable of absorbing and/or retaining fluid, e.g.,by capillary action. Alternatively, the fiber 704 may carryde-endothelialization agents that are chemically or physically attachedto the fiber 704.

FIG. 48 shows a variation of the de-endothelialization device 700 inwhich the fiber 704 is substantially longitudinally oriented and issecured to the core member 702 at one or more locations 706 along alength of the core member 702. FIG. 49 shows another variation of thede-endothelialization device 700 in which one or more fibers 704 arearranged into a mesh that is secured to the core member 702. Thefiber(s) 704 may be arranged in a variety of patterns and are notlimited to those shown previously.

The core member 702 may be made from a variety of materials. In general,any of the materials discussed previously with reference to the coremember 12 of FIG. 1 is also applicable the core member 702 of thede-endothelialization device 700. The core member 702 may also assume avariety of shapes. Any of the shapes discussed previously with referenceto FIGS. 1-11 may also be used.

When using the de-endothelialization device 700, thede-endothelialization device 700 may be dipped into ade-endothelialization fluid, which may be absorbed and/or otherwiseretained by the fiber 704 of the de-endothelialization device 700. Thede-endothelialization device 700 may then be delivered to an aneurysm orother body lumen using any of the methods described previously withreference to FIGS. 12-15, or any conventionally known method. After thede-endothelialization device 700 contacts the endothelium of theaneurysm or other body lumen, the fluid 350 then causes the endotheliumto be disrupted, as discussed previously.

It should be noted that instead of using the de-endothelializationdevice 700 described previously, a similar procedure may be completedusing any implantable object, such as a vaso-occlusive device. Inparticular, a vaso-occlusive device may be dipped intode-endothelialization fluid, which may then adhere to a surface of thevaso-occlusive device by surface adhesion. The vaso-occlusive device,carrying the fluid, may then be delivered to an aneurysm or other bodylumen.

FIG. 50 shows another de-endothelialization device 720 that includes acore member 722 and a coating 724 secured to the core member 722. Thecoating 724 is preferably secured to the core member 722 duringmanufacturing. However, the coating 724 may also be applied on the coremember 722 by a user immediately before a procedure. The coating 724 maybe applied to the core member 722, for example, by dipping the coremember 722 into a solution. The coating 724 may contain similarde-endothelializing ingredients, such as a cytotoxic agent, as that ofde-endothelialization fluids described above. When thede-endothelialization device 720 is placed within an aneurysm, a bodytemperature and/or a chemical reaction may be used to degrade ordissolve the coating 724 to release the de-endothelializing ingredients.When the endothelium of the aneurysm or other body lumen is contacted bythe de-endothelializing ingredients, the endothelium is then disrupted.

De-endothelialization fluid 350 may also be delivered via a hydrogelcoating. FIG. 51 shows a de-endothelialization device 730 having ahydrogel coating 732 coupled to a core member 734. The hydrogel coating732 is capable of absorbing a desired amount of de-endothelializationfluid. Examples of hydrogels include gels formed from polysaccharides,mucopolysaccharides, polyaminoacids, proteins that support cell growthand healing, polyphosphazines, polyphosphoesters, polyethylene glycol,polyethylene oxide, polyvinyl alcohol, polyvinylpyrrolidone,polyethyloxazoline, polyethylene oxide-co-polypropyleneoxide blockcopolymers, PGA-PEG-PGA block copolymers, PGA-PEG diblock copolymers,acrylates, carboxy alkyl celluloses, partially oxidized cellulose,polymers and oligomers of glycolide and lactide, polylactic acid,polyesters of .alpha.-hydroxy acids, polylactones, polycaprolactones,polyanhydrides, polyorthoesters, polydioxanone, styrene, acrolein andcombinations thereof. Other examples of hydrogels may also include gelsformed from hyaluronic acid, dextran, heparin sulfate, chondroitinsulfate, heparin, agar, starch, alginate, fibronectin, gelatin,collagen, fibrin, pectins, albumin, ovalbumin,collagen-hydroxyethyl-methacrylate (HEMA); diacrylates, oligoacrylates,methacrylates, dimethacrylates, oligomethoacrylates,PEG-oligoglycolylacrylates, carboxymethyl cellulose, polyesters oflactic acid, polyesters of glycolic acid, poly(.alpha.-hydroxy) acidsincluding polyglycolic acid, poly-DL-lactic, poly-L-lactic acid, andterpolymers of DL-lactide and glycolide, .epsilon.-caprolactone,.epsilon.-caprolactone copolymerized with polyesters,poly(.epsilon.-caprolactone), poly(.delta.-valerolactone),poly(gamma-butyrolactone), and combinations thereof. When using thede-endothelialization device 730, the de-endothelialization device 730is first dipped into de-endothelialization fluid. Due to the absorptivecharacteristic of the hydrogel coating 732, the hydrogel coating 732absorbs the fluid and retains the fluid within the coating 732.

The endothelialization device 730 may then be delivered to an aneurysmor other body lumen using any of the methods discussed previously. Oncesituated inside the sac of the aneurysm or at the site of another bodylumen, the fluid may diffuse from the hydrogel coating 732 and contactthe endothelium of the aneurysm or other body lumen to disrupt theendothelium.

Although several embodiments and methods of de-endothelializing ananeurysm or other body lumen have been described, it should be notedthat one or more of the above described embodiments may be combined withanother. For example, the de-endothelialization device 10 described withreference to FIGS. 1-11 may also be heated and/or dipped intode-endothelialization fluid to enhance its de-endothelializationproperties. Also, the de-endothelialization device 300 describedpreviously with reference to FIG. 30 can also include an abrasiveelement 14, such as that shown in FIG. 1, to enhance itsde-endothelialization property. Combination of other embodimentsdescribed previously may also be used.

Furthermore, although the embodiments have been discussed with referenceto treating aneurysms, the scope of the invention should not be solimited. For example, any of the above described embodiments may also beused to de-endothelialize vascular tissue for treating arteriovenousmalformations (AVMs), arteriovenous fistulas (AVFs), or other vascularconditions. Other bodily tissues may also be de-endothelialized fortreatment of various medical conditions, such as tumors, using any ofthe above discussed devices and/or methods.

Thus, although several preferred embodiments have been shown anddescribed, it would be apparent to those skilled in the art that manychanges and modifications may be made thereto without departing from thescope of the invention, which is defined by the following claims andtheir equivalents.

1. An apparatus for disrupting an endothelium of an aneurysm, anarterio-venous malformation, or a fistula, the apparatus comprising: anouter member having a proximal end and a distal end, the distal endhaving a size and shape for insertion into a body lumen; an inner memberdeployable from within the outer member and comprising a proximal end, adistal end, and a first lumen extending between the proximal end and anoutlet port on the distal end; and a source of de-endothelializationfluid coupled to the proximal end of the inner member and communicatingwith the first lumen.
 2. The apparatus of claim 1, wherein thede-endothelialization fluid is a cytotoxic agent comprising a hypotonicfluid.
 3. The apparatus of claim 1, wherein the distal end of at leastone inner and outer members includes an aspiration port and wherein atleast one of the inner and outer members comprises a second lumencommunicating with the aspiration port and a source of vacuum foraspirating fluid from the treatment site.
 4. The apparatus of claim 3,further comprising a sealing member carried by one of the inner andouter members proximal to the outlet port, the sealing member having asize and shape for substantially sealing the body lumen, wherein theaspiration port is disposed distal to the sealing member.
 5. Theapparatus of claim 1, further comprising a coil extending from thedistal end of the inner member, the coil configured for directing fluiddelivered from the outlet port in a desired pattern within the treatmentsite.
 6. The apparatus of claim 1, further comprising a balloon carriedon the distal end of the inner member, the balloon having the outletport thereon.
 7. The apparatus of claim 6, wherein the outlet portcomprises one or more openings extending through a wall of the balloonand communicating with an interior of the balloon, the interior of theballoon communicating with the first lumen, the one or more openings ofthe balloon sized such that when the balloon is inflated by thede-endothelialization fluid, the one or more openings expandsufficiently to allow the de-endothelialization fluid to exit from theinterior of the balloon through the one or more openings.
 8. Theapparatus of claim 6, wherein the balloon comprises a delivery lumenformed within a wall of the balloon communicating with the outlet portand the first lumen.
 9. An apparatus for disrupting an endothelium of abody lumen, comprising: an elongate tubular member comprising a proximalend and a distal end having a size and shape for insertion into a bodylumen, the tubular member comprising an infusion lumen and an aspirationlumen extending between the proximal and distal ends; a first fluidmoving element communicating with the infusion lumen of the tubularmember; a second fluid moving element communicating with the aspirationlumen of the tubular member; an actuator coupled to the first and secondfluid moving elements, the actuator configured for simultaneouslydelivering fluid into the infusion lumen and withdrawing fluid from theaspiration lumen; and a source of de-endothelialization fluidcommunicating with the first lumen.
 10. The apparatus of claim 9,wherein the de-endothelialization fluid is a cytotoxic agent comprisinga hypotonic fluid.
 11. The apparatus of claim 9, wherein the tubularmember comprises a first tubular member having a first lumen therein anda second tubular member within the lumen of the first tubular member,and wherein one of the infusion and aspiration lumens is defined betweenthe first and second tubular members, and the other of the infusion andaspiration lumens is a lumen within the second tubular member.
 12. Theapparatus of claim 9, further comprising an occlusion member associatedwith the tubular member for substantially sealing the body lumen. 13.The apparatus of claim 12, wherein the occlusion member comprises anexpandable member carried on the distal end of the tubular member. 14.The apparatus of claim 12, wherein the occlusion member comprises anexpandable member carried on a distal end of an elongate member.
 15. Theapparatus of claim 14, wherein the expandable member comprises acompliant balloon, the balloon comprising a side port, wherein one ofthe infusion and aspiration lumens communicates with the side port. 16.The apparatus of claim 9, wherein the actuator comprises a motor.
 17. Anapparatus for disrupting an endothelium of a body lumen, comprising: atubular member comprising a proximal end, a distal end having a size andshape for insertion into a body lumen, and first and second lumensextending between the first and second lumens; a source ofde-endothelialization fluid coupled to the proximal end of the tubularmember and communicating with the first lumen for delivering thede-endothelialization fluid to tissue adjacent the distal end to atleast partially de-endothelialize the tissue; and a source of vacuumcoupled to the proximal end of the tubular member and communicating withthe second lumen for aspirating excess de-endothelialization fluid froma region adjacent the distal end of the tubular member.
 18. Theapparatus of claim 17, wherein the de-endothelialization fluid is acytotoxic agent comprising a hypotonic fluid.